•Long-term cancer survivors are at increased risk of mood disorders particularly in the first 2 years after diagnosis.•The magnitude of risk of mood disorders varied by cancer subtype as well as by the severity of comorbidities, socioeconomic factors and cancer-related factors such as the number of primary cancer and cancer treatment.•Patients with head and neck cancer and esophageal cancers had greater risk of mood disorders after 5 years of follow-up (data not shown), indicating that the need of psychological care for late follow-up of certain cancer subtypes. The increasing number of long-term cancer survivors over the past few decades poses the challenge of mental health care needs. However, little is known about risks of mood disorders in long-term cancer survivors. Long-term survivors (≥5 years) of adult cancers (LSAC) (n = 190,748) newly diagnosed between January 1, 2000 and December 31, 2007 were matched with one control. The primary outcome was diagnosis of mood disorders requiring psychotropics. Cumulative incidences and sub-hazard ratios (SHR) were calculated and multivariate analyses were conducted after accounting for mortality. The mood disorder risk was significantly higher in the LSAC cohort than in the control cohort (adjusted SHR = 1.16, 95% confidence interval CI = 1.13–1.18, P < 0.001). Patients with certain cancer types were at increased risk, particularly in the first 2 years after diagnosis. However, patients with head and neck cancers or esophageal cancers had a higher risk after the 5-year follow-up period. Multivariate analysis indicated that being female, aged 40–59 years, with more than two primary cancers, receiving two or more treatment modalities, having CCI scores higher than 3, a higher urbanization level, and lower monthly income were independently associated with an increased risk of mood disorders. Some potential confounders such as lifestyle factors were not available in the study. These findings call for increased mental health awareness not only in the early years after the cancer diagnosis, but also during long-term follow-up for certain cancer subtypes.