Background: This study examined the moderating effect of emotional support from acquaintances and the mediating effect of disability acceptance in the association between disability-related negative experiences and depression in disabled people with cancer.Methods: Data were collected from 295 participants in the“Disabled-Life Panel Research” conducted by the Korea Disabled people’s Development Institute. The collected data were analyzed using SPSS Windows 26.0 with the PROCESS Macro program 4.0 as a moderated mediating model. Results: Higher disability-related negative experiences caused lower disability acceptance, which predicted higher depression levels. Emotional support played a significant moderating role in this relationship. The effect of negative experiences on disability acceptance was weaker in disabled individuals with cancer who perceived higher social support from acquaintances.Conclusions: These results suggest that focusing on emotional support is important in protecting the psychological health of disabled people with cancer who are alienated from society.