Pre-exposure prophylaxis (PrEP) is a promising HIV prevention method. However, the rollout of PrEP among men who have sex with men (MSM) is facing challenges. This study sought to understand PrEP acceptability and service use challenges among MSM in China. The study was conducted in 2018 in Guangdong Province using a mixed-methods approach. Among 489 HIV-negative MSM who completed an online survey, 374 (76.5%) had heard of PrEP before. The most common PrEP information sources were internet/social media (32.1%) and community-based organizations (30.4%). Two-thirds (n=328) of the MSM would accept PrEP even the protective efficacy is less than 100%, 60.1% (n=294) expressed willingness to use PrEP once it is approved in China, and 59.3% (n=290) were willing to pay out of pocket. Employment, disclosure of MSM status, and mental health issues were associated with PrEP acceptability. In-depth interviews with 30 MSM revealed that high cost, low accessibility, and stigma in clinic settings were barriers to PrEP using. Primary care-based PrEP services were acceptable, but patients' confidentiality was a concern. PrEP promotion efforts should address social and mental health challenges among MSM and mobilize primary care systems and community-based organizations to achieve the best result.