Background The outbreak of coronavirus disease MESHD-2019 (COVID-19) ineluctably caused social distancing and unemployment, which may bring additional health risks for patients with cancer. To investigate the association of the pandemic-related impacts with the health-related quality of life (HRQoL) among patients with melanoma MESHD melanoma HP during the COVID-19 pandemic, we conducted a cross-sectional study among Chinese patients with melanoma MESHD melanoma HP.Methods A self-administered online questionnaire was distributed to melanoma MESHD melanoma HP patients through social media. Demographic and clinical data, and pandemic-related impacts (unemployment and income loss) were collected. HRQoL was determined by the Functional Assessment of Cancer Therapy-General (FACT-G) and its disease MESHD-specific module (the melanoma MESHD melanoma HP subscale, MS).Results A total of 70 patients with melanoma MESHD melanoma HP completed the study. The mean age TRANS of the patients was 55.2 ± 14.8 years, 45.7% (32/70) were male TRANS, and 21.4% (15/70) were unemployed since the epidemic. Unemployment of the patients and their family members TRANS and income loss were significantly associated with a lower FACT-G score, while the MS score was associated with the unemployment of the patients’ family members TRANS.Conclusions Our findings suggested that unemployment is associated with impaired HRQoL in melanoma MESHD melanoma HP patients during the COVID-19 epidemic.