Allowing students to voluntarily ask and answer questions in front of the whole class are common teaching practices used in college science courses. However, few studies have examined college science students’ perceptions of these practices, the extent to which students choose to engage in these practices, and what discourages students from participating. In this study, we surveyed 417 undergraduates at a research-intensive institution about their experiences asking and answering questions in large-enrollment college science courses. Specifically, students answered questions about to what extent they perceive voluntarily asking and answering questions in large-enrollment science courses is helpful to them and why. They also answered questions about to what extent they engage in asking and answering questions in large-enrollment college science courses and what factors could discourage them from participating. Using binary logistic regression, we examined whether there were differences among students of different demographic groups regarding their opinions about asking and answering questions. We found that overwhelmingly students reported that other students voluntarily asking and answering instructor questions is helpful to them. Notably, compared to continuing generation students, first-generation students were more likely to perceive other students asking questions to be helpful. Despite perceiving asking and answering questions to be helpful, over half of students reported that they never ask or answer questions in large-enrollment college science courses during a semester, and women were more likely than men to report never asking questions. We identified fear of negative evaluation, or students’ sense of dread associated with being unfavorably evaluated, as a primary factor influencing their decision to answer instructor questions. This work adds to a growing body of literature on student participation in large-enrollment college science courses and begins to uncover underlying factors influencing student participation.