OBJECTIVE: This study aimed to explore the mediating roles of mindfulness and illness perception in the effects of a social media-based Mindfulness psyCho-behAvioRal intErvention (MCARE) on depressive and anxiety symptoms among patients with ACS. METHODS: This study conducted a secondary longitudinal mediation analysis using data from a randomized controlled trial of the MCARE grogram in patients with ACS. Participants were recruited at two tertiary hospitals in Jinan, China. The MCARE program consisted of six weekly sessions addressing mindfulness training and disease management to facilitate understanding and management of emotions and illness. The analytical sample included participants who completed measures of the primary outcomes, i.e., depression (PHQ-9) and anxiety (GAD-7) and potential mediators, i.e., mindfulness (CAMS-R) and illness perception (Brief-IPQ) at baseline (T0), immediate post-intervention (T1), and 12-week after the commencement of the intervention (T2). RESULTS: This study included 146 participants (mean age 58.9 years (SD = 8.9), 69.2 % male), including both intervention and control groups. The mediation analysis revealed a significant mediating effect of T1 mindfulness in the relationship between the group and T2 depression symptoms (indirect effect: -0.109, 95 % CI: -0.191, -0.041; P = 0.004), accounting for 26 % of the effect. For T2 anxiety symptoms, T1 illness perception exhibited a significant mediating effect (indirect effect: -0.055, 95 % CI: -0.110, -0.005; P = 0.035), accounting for 22 % of the effect. CONCLUSIONS: This study found that mindfulness and illness perception played a mediating role in the effects of the MCARE program on depressive and anxiety symptoms among patients with ACS.