One of the most uncomfortable moments in an interview is when the interviewer asks a question and you genuinely don't know the answer. The key is to be honest without undermining yourself: don't bluff, but don't shut down either.
I recently talked with two students who had just finished their job interviews, and both were unsure how they should have handled questions they couldn't answer.
So, what should you actually say when you don't know?
When I first started interviewing for industry jobs, I thought not knowing an answer would make me look incompetent. After working in industry R&D for five years, I’ve realized that scientists regularly encounter problems that require more data, experiments, or input from others.
The important question isn't always “Do you know the answer?”
Sometimes it is:
“How do you respond when you don't know?”
It’s okay not to know everything—but context matters
Not knowing an answer doesn't automatically mean you're unqualified. However, there is a difference between forgetting a specific detail and lacking a fundamental skill required for the role.
For example, you may not remember the exact setting from an experiment you completed several years ago. But if you're interviewing for a position that requires a specific technical skill, you should be able to explain its basic principles.
This is why you should thoroughly review everything on your resume before an interview. Be prepared to explain the key concepts, your contribution, and major experimental decisions behind the work you list.
Two common situations
1. You don't remember a factual detail
For example:
“What excitation wavelength did you use for this experiment?”
If you don't remember the exact number, don't make one up.
You could say:
“I don't remember the exact wavelength off the top of my head. I do remember the fluorophore and instrument configuration we used, and I could verify the exact setting from our experimental records.”
You're being honest about what you don't remember while demonstrating what you do know.
2. You don't know how to solve a technical problem
An interviewer might ask:
“Suppose this assay suddenly shows a significant increase in background. How would you troubleshoot it?”
You may never have encountered exactly this problem before. Instead of trying to guess the “correct” answer, explain your thinking.
For example:
“I haven't encountered that exact situation before, so I wouldn't want to assume the cause. I would first determine whether the issue is related to the assay, sample preparation, or instrument. I would compare the affected samples with an appropriate control and then check factors such as reagent quality, incubation conditions, and instrument performance.”
You may not have given a definitive answer, but you demonstrated that you know how to approach a problem.
For many R&D roles, that's an important part of being a scientist.
A simple framework: Show how you think
When you don't know an answer, remember:
Pause → Clarify → Acknowledge → Connect → Reason → Verify
Pause: Take a few seconds to think.
Clarify: Make sure you understand the question.
Acknowledge: Be specific about what you don't know.
Connect: Identify relevant knowledge or experience.
Reason: Explain how you would approach the problem.
Verify: Explain how you would confirm or learn the answer.
For example:
“I haven't worked directly with that technique, but I've worked with a similar approach, so I understand the underlying principle. Based on that experience, I would first look at X and Y. I would then check Z to determine which explanation is most likely.”
This is much stronger than simply saying, “I don't know.”
What you should NOT do
Don't bluff or make things up.
Especially in technical interviews, your interviewer may have much deeper expertise in the subject. A confident but incorrect answer can quickly damage your credibility.
Don't shut down.
If you have relevant knowledge or a reasonable way to approach the problem, show it.
Don't ramble or guess confidently.
It's fine to propose a hypothesis, but make it clear when you're making an assumption:
“My initial thought is X, but I would want to verify that because I haven't encountered this exact situation before.”
Reasoning is valuable; rambling is not.
The key takeaway
When you don't know an interview answer:
Don't bluff. Don't shut down. Show how you think.
Be honest about the gap, show what you do know, explain how you would approach the problem, and communicate how you would verify the answer.
You don't need to know everything to be a strong candidate. But you should demonstrate sound judgment about what you know, what you don't know, and how you would find out.
Good luck with your next interview!