This study aimed to analyze the epidemiological characteristics and spatiotemporal clustering of hepatitis A in mainland China from 2004 to 2019 and to evaluate the practical impact of integrating hepatitis A vaccines into the Expanded Program on Immunization (EPI). Spatial and temporal autocorrelation and spatiotemporal scanning statistics were used to perform spatial and temporal characterization to quantify the spatial similarity or degree of aggregation of geographic data, and Geographical and Temporal Weighted Regression (GTWR) models were used to reveal spatial and temporal heterogeneity in the relationships between variables to test for spatial and temporal outbreaks of disease and other factors, such as socio-economic factors. Spatially, the incidence rates exhibited a west-high and east-low spatial differentiation, with the High-High (HH) clusters predominantly located in the western regions, maintaining stability butgradually diminishing. Hepatitis A prevalence peaked during the initial study period (2004-2008) showing significant spatial clustering. However, since the inclusion of hepatitis A vaccine in the immunization program in 2008, the incidence rates of hepatitis A in mainland China significantly decreased demonstrating the positive impact of immunization strategies. In addition to the effects of vaccination, socio-economic factors such as education level, water resources and age groups showed significant associations with hepatitis A incidence rates. Increased vaccine coverage and improved social conditions are crucial for controlling hepatitis A in China.