BACKGROUND: Chemsex engagement is known to be associated with higher-risk sexual behaviour, HIV and sexually transmitted infection (STI). To reduce HIV infection risk, pre-exposure prophylaxis (PrEP) is increasingly used in the men who have sex with men (MSM) community. This study aims to examine the interrelationship between chemsex engagement and PrEP use in MSM. METHODS: This is a cross-sectional study with the recruitment of MSM in the community in Hong Kong. Participating MSM were invited to complete an online survey which included PrEP (experienced or naïve) use, chemsex engagement history and HIV test results. Chemsex engagement referred to use of specific drugs (methamphetamine and/or gamma-hydroxybutyrate) before and/or during sex. Characteristics of MSM with and without history of chemsex engagement were examined in bivariable and multivariable logistic regression. In a case-control analysis with a 1:1 ratio of PrEP-naïve and PrEP-experienced MSM, the association of chemsex engagement with history of PrEP use was examined in bivariable and multivariable logistic regression. RESULTS: Between February 2022 and January 2024, 338 eligible MSM were recruited. A higher proportion of MSM engaged in chemsex reported history of PrEP use and group sex. Prevalence of ever chemsex engagement was significantly higher in PrEP-experienced (29%) than PrEP-naïve MSM (9%) (adjusted OR=2.69, 95% CI 1.28 to 5.67), after adjustment for confounders of age, history of STI testing, multiple sex partnership and inconsistent condom use. The history of chemsex engagement in the past 6 months was associated positively with ever and recent (6 months) use of PrEP. Five out of seven PrEP-naïve MSM who had engaged in chemsex in the past 6 months indicated their intention to take PrEP. CONCLUSIONS: Chemsex engagement was positively associated with PrEP use while most of the PrEP-naïve MSM who had recently engaged in chemsex expressed interest to start PrEP. PrEP service could be an important community platform for chemsex intervention.