BACKGROUND AND AIM: Physical activity (PA) may increase the inhalation and deposition of air pollutants, possibly reducing its beneficial effects. We thus examined the combined effects of chronic exposure to fine particle matter (PM2.5) and habitual PA on the risk of cancer mortality in Taiwan. METHODS: A total of 384,128 adults (≥18 years) with 842,384 medical examinations were recruited between 2001 and 2016. All participants were followed up until May 31, 2019. Vital data were obtained from the National Death Registry of Taiwan. Ambient PM2.5 exposure was estimated using a satellite-based spatiotemporal model. Information on habitual PA was collected using a standard self-administered questionnaire. The time-dependent Cox regression model was used to evaluate the combined effects. RESULTS:Higher habitual PA was associated with lower risk of cancer mortality, whereas higher PM2.5 exposure was associated with higher risk of cancer mortality. The inverse associations of habitual PA with cancer mortality were not modified by chronic exposure to PM2.5. Compared to the participants with inactive-low-PA and high-PM2.5, those with high-PA and low-PM2.5 exhibited a 35% lower risk of cancer mortality [95% confidence interval (CI): 28%-42%]. CONCLUSIONS:Increased PA and reduced PM2.5 exposure are associated with lower risk of cancer mortality. Habitual PA reduces the risk of cancer mortality regardless of the levels of chronic PM2.5 exposure. Our results indicate that habitual PA is a suitable health promotion strategy even for people residing in relatively polluted regions. KEYWORDS: Particulate matter, Long-term exposure, cancer mortality