BACKGROUND: The growth in mobile technology access, utilization, and services holds great promise in facilitating HIV prevention efforts through mobile health (mHealth) interventions in Malaysia. Despite these promising trends, there is a dearth of evidence on the use of mHealth platforms that addresses HIV prevention among Malaysian men who have sex with men. OBJECTIVE: The goal of this study was to gain insight into (1) access and utilization of communication technology (eg, landline phone, internet, mobile phone), (2) acceptability of mHealth-based interventions for HIV prevention services, and (3) preferences regarding the format and frequency of mHealth interventions among Malaysian men who have sex with men. METHODS: We conducted a cross-sectional survey with Malaysian men who have sex with men between July 2018 and March 2020. Participants were recruited using respondent-driven sampling in the Greater Kuala Lumpur region of Malaysia. We collected information on demographic characteristics, HIV risk-related behaviors, access to and the frequency of use of communication technology, and acceptability of using mHealth for HIV prevention using a self-administered questionnaire with a 5-point scale (1, never; 2, rarely; 3, sometimes; 4, often; 5, all the time). RESULTS: A total of 376 men participated in the survey. Almost all respondents owned or had access to a smartphone with internet access (368/376, 97.9%) and accessed the internet daily (373/376, 99.2%), mainly on a smartphone (334/376, 88.8%). Participants on average used smartphones primarily for social networking (mean 4.5, SD 0.8), followed by sending or receiving emails (mean 4.0, SD 1.0), and searching for health-related information (mean 3.5, SD 0.9). There was high acceptance of the use of mHealth for HIV prevention (mean 4.1, SD 1.5), including for receiving HIV prevention information (345/376, 91.8%), receiving medication reminders (336/376, 89.4%), screening and monitoring sexual activity (306/376, 81.4%) or illicit drug use (281/376, 74.7%), and monitoring drug cravings (280/376, 74.5%). Participants overwhelmingly preferred a smartphone app over other modalities (eg, text, phone call, email) for engaging in mHealth HIV prevention tools. Preference for app notifications ranged from 186/336 (53.9%), for receiving HIV prevention information, to 212/336 (69.3%), for screening and monitoring sexual activity. Acceptance of mHealth was higher for those who were university graduates (P=.003), living in a relationship with a partner (P=.04), engaged in sexualized drug use (P=.01), and engaged in receptive anal sex (P=.006). CONCLUSIONS: Findings from this study provide support for developing and deploying mHealth strategies for HIV prevention using a smartphone app in men who have sex with men-a key population with suboptimal engagement in HIV prevention and treatment.