Rural residents have lower levels of engagement in health-promoting behaviors and treatment adherence than their urban counterparts. This cross-sectional study sought to understand the role of health self-efficacy as a precursor to engagement in health-promoting behaviors and treatment adherence in 273 rural patients. Structural equation model was used to examine whether health self-efficacy predicted engagement in health-promoting behaviors and treatment adherence. Results show that health self-efficacy predicts engagement in health-promoting behaviors and treatment adherence. Boosting patients' health self-efficacy could be a way of increasing their engagement in health-promoting behaviors and treatment adherence and thus of improving their health outcomes.