OBJECTIVES: Skin cancer is one of the most common cancers in the United States (US).  Studies have reported depression to be a common comorbid condition among individuals with cancer. This study aimed to evaluate the relationship of depression with health-related quality of life (HRQOL) among individuals with skin cancer diagnosis. METHODS: A cross-sectional study design using the 2014 Behavioral Risk Factor Surveillance System (BRFSS) data, a nationally representative sample of non-institutionalized US adults, was utilized for the study analysis. Multivariable logistic regression was used to assess the relationship between depression and the various domains of HRQOL (general health status, physical health, mental health, and activity limitations due to poor physical or mental health) among survivors of skin cancer. SAS version 9.4 was used for the survey analyses (PROC SURVEY). RESULTS: The prevalence of comorbid depression was around 21% among skin cancer survivors. After adjusting for all covariates, skin cancer survivors with depression had lower odds of having good general health status (Odds Ratio [OR] = 0.56, Confidence Interval [CI] 0.49-0.64) as compared to skin cancer survivors without depression. Skin cancer survivors with depression were also less likely to experience good (< 14 unhealthy days) physical HRQOL (OR = 0.56, CI 0.48-0.64), mental HRQOL (OR = 0.13, CI 0.11-0.16), and less activity limitations (OR = 0.45, CI 0.38-0.52) as compared to those without depression. CONCLUSIONS: This study highlights the significant negative impact of comorbid depression on HRQOL among skin cancer survivors. Depression screening and management should be included as part of skin cancer treatment profile.