Background: Oral pre-exposure prophylaxis (PrEP) is recommended as an additional prevention choice for men who have sex with men (MSM) at substantial risk of HIV. The aim of this study was to evaluate the extent, and reasons, for MSM’s willingness to use oral PrEP in Wuhan and Shanghai, China. Methods: Between May and December 2015, a cross-sectional survey was conducted among 487 MSM recruited through snowball sampling in physical locations frequented by MSM and through social media applications. Exploratory factor analysis was used to group reasons for being willing or not willing to use PrEP. Chi-square tests were used to explore bivariate associations between groupings of reasons for being willing or unwilling to use PrEP, and key sociodemographic and sexual-behavioral characteristics of MSM. Results: Overall, 71.3% of respondents were willing to use PrEP. The most commonly reported reasons for being willing to use PrEP were preventing HIV infection (91.6%), taking responsibility for own sexual health (72.6%) and protecting family members from harm (59.4%). The main reasons for being unwilling to use PrEP were being worried about side effects (72.9%), the necessity of taking PrEP for long periods of time (54.3%) and cost (40.4%). Individual characteristics that influenced the type of reasons given for being willing or unwilling to use PrEP included being married to a woman, having a regular sex partner, rates of condom use with regular and casual sex partners, and the number of casual sex partners. Conclusion: The introduction of PrEP in China could benefit from promotion campaigns that emphasize its role in preventing HIV infection, in taking responsibility for own sexual health, and in protecting family members from potential harm. To reduce uptake barriers, it will be essential to provide accurate information to potential PrEP users about the mild and short-term nature of side effects, and the possibility of taking PrEP only during particular periods of life when the risk of HIV exposure might be highest.