<p>Previous studies have shown that the hope of breast cancer patients is related to the social relational quality, and personality is related to acceptance of disability. However, research is still unclear about the underlying potential psychological mechanisms of various psycho-social factors for this population. This study aims to investigate the impact of breast cancer patients’ hope and type C personality on social relational quality and acceptance of disability, and to evaluate the mediating the role of medical coping styles. A total of 141 breast cancer patients during chemotherapy were recruited from Harbin, China completed a self-reported questionnaire containing the personal information questionnaire, Herth hope index (HHI), Type C behavior scale, Medical coping modes questionnaire (MCMQ), Social relationship quality scale (SRQS) and Acceptance of disability scale (ADS). Results showed that the proposed model fitted the data very well (χ² = 8.357, df = 7, p = 0.302, χ²/df = 1.194, GFI = 0.981, CFI = 0.991, TLI = 0.982, RMSEA = 0.037). Further analyses revealed that, confrontation mediated the relationship between hope and social relational quality (indirect effect = 0.025, BC 95%CI = 0.001, 0.079), and acceptance-resignation mediated the relationship between type C personality and acceptance of disability (indirect effect = − 0.109, BC 95%CI = − 0.188, − 0.044). Confrontation and acceptance-resignation played critical roles in the relationship between hope, type C personality and social relational quality, the acceptance of disability of breast cancer patients. Healthcare practitioners should be aware of the coping strategies of breast cancer patients, and psycho-social interventions and supportive care should focus on these cognitive and emotional processes to improve social relational quality and acceptance of disability for this population.</p>