Skin diseases have caused a heavy burden on the infected population worldwide. This study aimed to examine the health-related quality of life (HRQOL) among patients with different skin diseases and identify associated factors. A cross-sectional study with 430 participants was conducted at the Vietnam National Hospital of Dermatology and Venereology (NHD) from September to November 2018. The EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) instrument was employed, which measures the EQ-5D index from five domains including mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Multivariate Tobit regression was adopted to determine factors that were associated with HRQOL (EQ-5D index). The rate of atopic dermatitis was the highest with 28.8%, following by contact dermatitis (17.0%) and skin fungal infections (13.0%). Regarding HRQOL, anxiety/depression was the most common health problem in patients with skin diseases (71.8%), following by pain/discomfort (63.6%). The mean EQ-5D index score was 0.73 (SD = 0.19). The lowest EQ-5D index scores were obtained for females with skin infections (mean = 0.52) and for males with psoriasis (mean = 0.59). Females had significantly lower scores compared to males (Coef. = -0.06; 95% CI = -0.11 to -0.01). Higher income and living in rural areas were also negatively correlated with the EQ-5D index. This study demonstrated the low HRQOL among patients with skin diseases in Vietnam and emphasized the vulnerability of patients with different socioeconomic statuses to their HRQOL.