PURPOSE: The aim of this study was to investigate the effects of a mindfulness-based day care clinic group program for cancer survivors on health-related quality of life and mental health; and to investigate which psychological variables are associated with changes in health variables. METHODS: One hundred seventeen cancer survivors (91.0 % female; mean age 53.9 ± 10.7 years; 65.0 % breast cancer; mean time since diagnosis 27.2 ± 46.5 months) participated in an 11-week mindfulness-based day care clinic group program, 6 h per week. The intervention incorporated mindfulness-based meditation, yoga, cognitive-behavioral techniques, and lifestyle modification. Outcome measures including health-related quality of life (EORTC QLQ-C30), depression and anxiety (HADS); and psychological variables including life satisfaction (BMLSS), mindfulness (FMI), adaptive coping styles (AKU), spiritual/religious attitudes in dealing with illness (SpREUK), and interpretation of illness (IIQ) were assessed before, after, and 3 months after the intervention. RESULTS: Using mixed linear models, significant improvements in global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning were found. Cancer-related symptoms, including fatigue, pain, insomnia, constipation, anxiety, and depression, also improved significantly. Mindfulness, life satisfaction, health satisfaction, all coping styles, all spiritual/religious attitudes, and interpretation of illness as something of value increased; interpretation of illness as punishment decreased significantly (all p < 0.05). Improved outcomes were associated with increases in psychological variables, mainly life satisfaction, health satisfaction, and trust in medical help (R (2) = 7.3-43.6 %). CONCLUSION: Supportive mindfulness-based interventions can be considered as an effective means to improve cancer survivors' physical and mental health. Functional improvements are associated with improved satisfaction and coping styles.