To examine the epidemiology of hepatitis B virus carrier status (HBVC) and sonographic fatty liver (SFL) in Taiwanese adults, and to evaluate their possible interaction in inducing liver damage (LD). >From an epidemiological viewpoint, we analyzed previous studies which indicated that fatty liver sensitizes host immune response to HBV infection and enhances liver damage. A cross-sectional retrospective analysis of health records including medical history, physical examination, abdominal sonogram, blood biochemistry and hepatic virological tests. We utilized the Student's t-test, chi-square, multivariate logistic regression and synergy index to assess risks for LD. Among a total of 5406 Taiwanese adults (mean age 46.2 years, 51.5% males), the prevalence of LD, HBVC and SFL were 12.3%, 15.1% and 33.4%, respectively; 5.1% of participants had SFL plus HBVC. Multivariate logistic regression analysis demonstrated that male gender (odds ratio (OR) = 2.8, 95% confidence interval (CI): 2.3-3.5), overweight state (OR = 1.6, 95% CI: 1.3-2.0), HBVC (OR = 2.5, 95% CI: 2.0-3.1) and SFL (OR = 4.2, 95% CI: 2.2-5.3) were independently associated with LD. Synergism analysis showed that the adjusted OR for LD in adults with HBVC-alone was 3.3 (95% CI: 2.4-4.6), SFL-alone, 4.7 (95% CI: 3.7-6.1) and combined HBVC and SFL, 9.5 (95% CI: 6.8-13.3); the synergy index was 1.4 (95% CI: 1.001-2.0). In Taiwanese adults, SFL plus HBVC have a significant synergistic association with LD.