OBJECTIVES: Cancer is related to lower health-related quality of life (HRQoL). However, little evidence exists regarding the marginal decrease in HRQoL by the presence of comorbid anxiety and mood disorders (bipolar and depressive disorders) among cancer survivors based on U.S population-based research. The objective of the study was to determine whether comorbid anxiety and mood disorders were associated decreased HRQoL among cancer survivors. METHODS: This cross-sectional study used data from the 2011 Medical Expenditure Panel Surveys (MEPS). The independent variable was the presence of anxiety and/or mood disorders, and the dependent variable was HRQoL, which was measured using the SF-12 physical health composite scale (PCS) and mental health composite scale (MCS). Descriptive statistics, chi-square tests, and generalized linear models (GLM) were used for analyses. RESULTS: Among the estimated 17,987,639 cancer survivors, 9.4% had anxiety but not mood mood disorders, 11.4% had mood disorders but not anxiety, 3.8% had both anxiety and mood disorders, and 75.7% had neither anxiety nor mood disorders. The chi-square tests shows that the prevalence of anxiety and/or mood disorders was significantly different by age groups (p<0.001), gender (p=0.002), and perceived health status (p<0.001), while it was not significantly different by race, insurance type, marital status, region, family income, and the presence of comorbidity. In the GLMs analyzing anxiety mood disorders separately, anxiety and mood disorders were both significantly associated with lower PCS scores (p=0.002 and p<0.001) and MCS scores (both p<0.001). After controlling for demographic and clinical factors, anxiety was not significantly associated with lower PCS scores (p=0.235), but was associated with lower MCS scores (p=0.005), and mood disorders were still significantly associated with both lower PCS (p=0.006) and MCS (p<0.001) scores. CONCLUSIONS: Both anxiety and mood disorders were independently associated with lower HRQoL among cancer survivors, but when controlling for other factors, mood disorders showed no association with the PCS.