BACKGROUND: Early detection of depression in cancer patients is essential for improving health outcomes. This study assessed the prevalence and determinants of depression among cancer patients and examined its association with social support. METHOD: A cross-sectional study was conducted at Al Amal Cancer Center, Al-Thawra Hospital, Hodeida City, Yemen (January-March 2023). Data on sociodemographic characteristics, depression (Patient Health Questionnaire, PHQ-9), and social support (Oslo Social Support Scale, OSSS-3) were collected. Multivariate binary logistic regression identified significant depression factors, and Pearson's correlation was used to assess the relationship between social support and depression. A p value of <
0.05 indicated statistical significance. RESULTS: Depression incidence among cancer patients was 55% (n = 192). Multivariate analysis revealed that married (AOR = 9.472, p <
0.001) and divorced/widowed patients (AOR = 11.649, p <
0.001) were more likely to have depression than single individuals were. Higher education (diploma or above) was protective (AOR = 0.071, p <
0.001). Elevated lipid levels were linked to a lower depression risk (AOR = 0.189, p = 0.003), and a family history of cancer (AOR = 4.239, p <
0.001), longer disease duration (>
4 years) (AOR = 3.197, p = 0.006), and difficulty in activities (AOR = 8.704, p <
0.001) increased depression risk. A significant negative correlation between depression and social support was found (r = - 0.237, p <
0.001). CONCLUSION: Over half of cancer patients experience depression, which is influenced by marital status, education, and disease-related factors. Social support significantly mitigates depression. IMPLICATIONS FOR PRACTICE: Enhancing social support and integrating mental health assessments by psychiatric professionals in oncology care is essential for improving the emotional well-being and overall quality of life of cancer patients.