Background:Dentistry is considered a difficult occupation. Hence, it could adversely influence the general health and life quality of dentists. Thus, the aim of this study was to evaluate the health-related quality of life (HR-QoL) and its relationship with gender, age, education level, systemic diseases, and job satisfaction among dentists in Semnan in 2015-2016. Methods: This cross-sectional study was conducted among dentists (61 general dentists and 15 dental specialists) in Semnan, Iran, in 2015 -2016. A checklist was used to collect information including gender, age, education level, systemic diseases, and job satisfaction. The HR-QoL was determined by the SF-36 questionnaire. Data were analyzed using SPSS 17 and t-test (P < 0.05).Results: Seventy-six dentists including 40 males (52.6%) and 36 females (47.4%) aged 26-69 years with a mean age of 41.5 ± 7.8 participated in the study. The dentists' HR-QoL was at an appropriate level (total score: 73.2 ± 10.8, physical component: 76.6 ± 12.8, mental component: 64.8 ± 16.0). Gender (males vs. females; P = 0.991), age ( < 35 vs. > 35 years; P = 0.892), education level (general dentists vs. dental specialists; P = 0.590), systemic diseases (with vs. without a systemic disease; P = 0.140), and job satisfaction (satisfied vs. unsatisfied; P = 0.199) revealed no significant effect on the HR-QoL. Conclusions: This study concluded that the dentists working in Semnan had an approximately high level of health-related quality of life.