ObjectiveThe objective of this study was to investigate the spatio-temporal distribution and epidemiological characteristics of hepatitis B in 96 districts and counties of Xinjiang and to give useful information for hepatitis B prevention and treatment.MethodsBased on the incidence data of hepatitis B in 96 districts and counties of Xinjiang from 2006 to 2019, the global trend analysis method was used to characterize the spatial variability of the disease, and the spatial autocorrelation and spatio-temporal aggregation analysis were used to explore the spatial clustering of hepatitis B and to identify high-risk areas and periods. The Integrated Nested Laplace Approximation (INLA)-based spatial age-period-cohort model was established to further explore the influence of age, period, birth queue effect, and spatial distribution on the incidence risk of hepatitis B, and sum-to-zero constraint was adopted to avoid the issue of model unrecognition.ResultsThe risk of hepatitis B in Xinjiang is increasing from west to east and from north to south, with spatial heterogeneity and spatio-temporal scanning statistics yielding five clustering areas. The spatial age-period-cohort model showed two peaks in the average risk of hepatitis B, at [25,30) years old and [50,55) years old, respectively. The mean risk of hepatitis B incidence fluctuated up and down around 1 with time, and the average risk of disease by birth cohort displayed an increasing-decreasing-stabilizing trend. Taking age, period, and cohort effect into consideration, it was found that the areas with a high risk of hepatitis B are Tianshan District, Xinshi District, Shuimogou District, Changji City, Aksu City, Kashi City, Korla City, Qiemo County and Yopurga County in Xinjiang. According to the spatio-temporal effect item, it was found that there are unobserved variables affecting the incidence of hepatitis B in some districts and counties of Xinjiang.ConclusionThe spatio-temporal characteristics of hepatitis B and the high-risk population needed to be taken into attention. It is suggested that the relevant disease prevention and control centers should strengthen the prevention and control of hepatitis B among young people while paying attention to middle-aged and older adult people, and strengthening the prevention and monitoring of high-risk areas.