Abstract: Objective: To examine the mediating effect of psychological resilience and self-efficacy on the relationship between social support and well-being in elderly patients with depression. Methods: Using convenience sampling, a total of 177 elderly patients hospitalized for depression at the Second Affiliated Hospital of Henan Medical University between March 2024 and August 2025 were enrolled. The following scales were used for assessment: the social support rating scale (SSRS), the Connor-Davidson resilience scale (CD-RISC), the general self-efficacy scale (GSES), and the general well-being schedule (GWB). Pearson correlation analysis and mediation effect modeling assessed relationships among variables. Results: The mean SSRS score for elderly patients with depression was (30.71±6.64), the mean CD-RISC score was (42.38±9.23), the mean GSES score was (25.43±1.69), and the mean GWB score was (64.73±12.67). Pearson correlation analysis revealed positive correlations between SSRS total scores and CD-RISC scores, GSES scores, and GWB scores (all P＜0.001). Structural equation modeling revealed that the indirect effect value of the path "SSRS score→CD-RISC score→GSES score" was 0.143 (95% CI: 0.062-0.286), accounting for 22.17% of the total effect (P＜0.05). The indirect effect value of the path "CD-RISC score→GSES score→GWB score" was 0.048 (95% CI: 0.008-0.114), accounting for 15.95% of the total effect (P＞0.05). The indirect effect value of the path "SSRS score→CD-RISC score→GSES score→GWB score" was 0.219 (95% CI: 0.128-0.357), accounting for 45.53% of the total effect (P＜0.05). Conclusion: Social support can significantly enhance the well-being of elderly patients with depression, partially by improving their psychological resilience and self-efficacy. Clinical interventions should focus on optimizing patients′ social support networks, strengthening their psychological resilience and self-efficacy, and jointly promoting the improvement of their well-being.