This study is aimed at investigating the awareness of and preferences for oral and long-acting injectable HIV preexposure prophylaxis (PrEP) and their associated factors among men who have sex with men (MSM) at high risk of HIV infection in southern China. A cross-sectional survey was conducted among 603 MSM who were recruited through a cohort study called the T2T Study at three sexual health clinics in Guangzhou, Shenzhen, and Wuxi, China, from 2017 to 2018. We collected information on HIV-negative participants' awareness of and willingness to use PrEP and its potential correlations. Univariate and multivariate logistic regressions were used for data analyses. A total of 550 HIV-negative MSM were enrolled in the study. Less than half of at-risk MSM (43.1%) had heard of PrEP before, and the rate of overall willingness to use PrEP was 65.8%, while MSM were more willing to use daily oral PrEP than long-acting injectable- (LAI-) PrEP (62.2% vs. 38.5%). MSM who had university degrees or above (aOR = 1.55, 95% CI: 1.01-2.37), used condoms during last anal sex (1.52, 1.01-2.29), and tested 3 times or more for HIV (2.45, 1.10-5.47) were more likely to be aware of PrEP. MSM who had use of gay dating apps (1.51, 1.02-2.23), ever participated in HIV- or sexually transmitted disease (STD-) related studies (1.91, 1.24-2.94), and had heard of PrEP (3.06, 2.06-4.54) were more willing to use any regimen of PrEP. MSM at high risk of HIV infection had low awareness of PrEP and moderate willingness to use PrEP. Further studies of the implementation and promotion of PrEP targeting at-risk MSM should be performed.