Background Pre-exposure prophylaxis (PrEP) is an effective HIV prevention measure. Clinicians play a crucial role in PrEP implementation, and their knowledge, attitudes, and career experience may affect their willingness to prescribe PrEP. However, little is known about the attitudes and willingness of clinicians to prescribe PrEP in countries without PrEP-specific guidelines. Objective We aimed to determine the factors associated with clinicians being willing to prescribe PrEP in China. Methods Between May and June 2019, we conducted an online cross-sectional survey of clinicians in 31 provinces across the six administrative regions in China on the WeChat smartphone app platform. Multivariable logistic regression was used to determine factors associated with willingness to prescribe PrEP. Results Overall, 777 HIV clinicians completed the survey. Most of the respondents had heard of PrEP (563/777, 72.5%), 31.9% (248/777) thought that PrEP was extremely effective for reducing the risk of HIV infection, and 47.2% (367/777) thought that it was necessary to provide PrEP to high-risk groups. After adjusting for age, gender, ethnicity, and educational background of the clinicians, the following factors significantly increased the odds of the clinicians being willing to prescribe PrEP: having worked for more than 10 years, compared to 5 years or less (adjusted odds ratio [aOR] 2.82, 95% CI 1.96-4.05); having treated more than 100 patients living with HIV per month, compared to 50 patients or fewer (aOR 4.16, 95% CI 2.85-6.08); and having heard of PrEP (aOR 7.32, 95% CI 4.88-10.97). Clinicians were less likely to be willing to prescribe PrEP if they were concerned about poor adherence to PrEP (aOR 0.66, 95% CI 0.50-0.88), the lack of PrEP clinical guidelines (aOR 0.47, 95% CI 0.32-0.70), and the lack of drug indications for PrEP (aOR 0.49, 95% CI 0.32-0.76). Conclusions About half of all clinicians surveyed were willing to prescribe PrEP, but most surveyed had a low understanding of PrEP. Lack of PrEP clinical guidelines, lack of drug indications, and less than 11 years of work experience were the main barriers to the surveyed clinicians’ willingness to prescribe PrEP. Development of PrEP clinical guidelines and drug indications, as well as increasing the availability of PrEP training, could help improve understanding of PrEP among clinicians and, thus, increase the number willing to prescribe PrEP.