The potential is high that you will face some form of the question "What is your biggest weakness?" in a job interview. The difficulty of the question actually presents an opportunity for you to impress the hiring manager. Though you may honestly lack confidence, answering with such a general and significant weakness isn't normally a good choice.
Scope of Weakness
It is much better to offer a narrow, or more specific weakness, according to a January 2013 "Forbes" article. A primary purpose of this question is to identify any areas of concerns with your background and ability to perform the job. The more narrow your response, the less likely it is that you will hit on a red flag. Lack of confidence is one of the broadest weaknesses that you can touch on, since this deficiency can impact all facets of your work.
Importance of Confidence
The more important a trait is to a given position, the more negative the impact if you identify it as a weakness. While saying you are "shy" in an interview for a public speaking role may have a more direct impact on getting that job, indicating that you lack confidence would likely affect a hiring manager's perception of you regardless of the job. Confidence is a particularly important quality that tends to help people in any profession. If a salesperson tells a hiring manager he lacks confidence, the manager will likely wonder how he could cold call, talk persuasively to total strangers, and assertively close deals.
The irony in using lack of confidence as your weakness is that a primary motive of the interview process is to assess your ability to perform under pressure. Across the entire process, the hiring manager wants to see if you have calm, poise and confidence while being examined. To say that you lack confidence essentially simplifies the hiring managers process of assessing your overall interview performance.
A better strategy is to review the important qualities that the employer lists for the position and compare them to your weaknesses. You want to provide a genuine response, but select a specific, narrow weakness unrelated to the critical needs of the job. Saying you struggle with structure and routine works well if you interview with a highly creative, informal employer. Even better, show an effort to grow with something like "I've struggled with highly routine jobs because I like creativity and variety, but I have learned to keep effective schedules and to concentrate through those experience."