Background <p>To explore whether the impact of community spiritual comfort service (CSCS) on cognitive function is mediated by social participation and moderated by genetic factors.</p> Methods <p>Data were derived from the Chinese Longitudinal Healthy Longevity Survey conducted in 2008, 2011, 2014, and 2018, involving 3598 participants. A Random Intercept Cross-Lagged Panel Model was utilized to determine the relationship between CSCS and cognitive function, as well as the mediating role of social participation and the moderating effect of genetics on the identified CSCS and cognitive function relationship.</p> Results <p>Lower levels of CSCS at earlier assessment points were significantly associated with lower cognitive function at subsequent assessment points. Social participation partially mediated the prospective relationship between CSCS and cognitive function. Distinct genetic polymorphisms showed significant differences in effect sizes, with the Val group experiencing a significantly greater impact of CSCS on subsequent social participation, and of social participation on subsequent cognitive function, compared to the Met group.</p> Conclusion <p>Enhancements in CSCS can predict subsequent improvements in cognitive function. The relationship between CSCS and cognitive function can be mediated by social participation and is moderated by genetic factors. Multidisciplinary interventions aimed at improving the quality of CSCS and enhancing social participation will benefit the cognitive and psychological health of the older adults.</p>