Background: This study was conducted to determine the mortality rate and years of life lost (YLL) due to homicide in Fars province. Study Design: This was a cross-sectional study. Methods: All data related to deaths due to homicide in Fars province were obtained from the Populationbased Electronic Death Registration System. Crude and age-standardized mortality rate, YLL, and YLL rate data were calculated and joinpoint regression was used to examine the trend. Results: During 2004-2019, 2148 deaths due to homicide occurred in Fars province, and (1782 cases (83.0%) were men. The crude mortality rate in men decreased by 44.0% from 2004 to 2019, but a stable trend was observed in women. The total YLL due to homicide during these 16 years was 43230 (1.37 per 1000 people) in men and 8931 (0.29 per 1000 people) in women. According to the joinpoint regression analysis, the 16-year trend of the YLL rate due to premature mortality in men was decreasing, and the annual percent change (APC) was -4.00% (95% confidence interval [CI]: -6.60 to -1.20, P=0.008). However, women demonstrated stable trends in this respect, and APC was -0.50% (95% CI: -3.10 to 2.20, P=0.704). Conclusion: The crude and standardized mortality rates and the number of YLL due to homicide in the study period had a significant decreasing trend in men but a stable trend in women. To control this issue, officials and policymakers should identify the areas of homicide and control its risk factors such as economic and social issues, drug addiction, and the state of violence.