BACKGROUND: Social support and self-efficacy are important factors to improve negative emotions such as depression and anxiety in patients with prostate cancer after surgery; however, little is known about the relationship between them. The objective of the study was to comprehensively explore the relationship between social support, self-efficacy, and anxiety and depression. METHOD: A cross-sectional design and a convenience sampling method were used to recruit patients with prostate cancer from a comprehensive hospital in Zhejiang Province. Structured scales were used for data collection, including the Social Support Rating Scale, Strategies Used by People to Promote Health, and the hospital anxiety and depression scale. RESULTS: The result showed that anxiety and depression were negatively correlated with self-efficacy (r =  - 0. 434, P < 0. 01) and social support (r =  - 0. 212, P < 0. 01), while self-efficacy and social support were positively correlated (r = 0. 356, P < 0. 01). A structural equation model showed that the effect value of social support on self-efficacy was (β = 0.386, p < 0.01) and the effect value of self-efficacy on negative emotions was (β =  - 0.497, p < 0.01). Self-efficacy fully mediated the effect between social support and negative emotions with a 100% mediation rate. CONCLUSION: Social support and self-efficacy did contribute to the improvement of depression and anxiety in patients with radical prostatectomy, and they were associated with a full mediating effect of self-efficacy. Providing social support that matches the coping needs of the stressor can maximize the role of social support. Therefore, it is necessary to identify the patient's stressor and coping needs in advance, which will help us to provide matching social support, so as to alleviate patients' bad emotions more effectively and improve their prognosis.