AIM: To investigate the population-based prevalence of fatty liver disease (FLD) and its risk factors in Guangdong Province, China. METHODS: A cross-sectional survey with multiple-stage stratified cluster and random sampling of inhabitants over 7-year-old was performed in 6 urban and rural areas of Guangdong Province, China. Questionnaires, designed by co-working of epidemiologists and hepatologists, included demographic characteristics, current medication use, medical history and health-relevant behaviors, i.e. alcohol consumption, smoking habits, dietary habits and physical activities. Anthropometric measurements, biochemical tests and abdominal ultrasonography were carried out. RESULTS: Among the 3543 subjects, 609 (17.2%) were diagnosed having FLD (18.0% males, 16.7% females, P > 0.05). Among them, the prevalence of confirmed alcoholic liver disease (ALD), suspected ALD and nonalcoholic fatty liver disease (NAFLD) were 0.4%, 1.8%, and 15.0%, respectively. The prevalence rate (23.0%) was significantly higher in urban areas than (12.9%) in rural areas. After adjustment for age, gender and residency, the standardized prevalence of FLD in adults was 14.5%. Among them, confirmed ALD, suspected ALD and NAFLD were 0.5%, 2.3%, and 11.7%, respectively, and 1.3% (all NAFLD) in children at the age of 7-18 years. The overall prevalence of FLD increased with age in both genders to the peak of 27.4% in the group of subjects at the age of 60-70 years. The prevalence rate was significantly higher in men than in women under the age of 50 years (22.4% vs 7.1%, P < 0.001). However, the opposite phenomenon was found over eth age of 50 years (20.6% vs 27.6%, P < 0.05). Multivariate and logistic regression analysis indicated that male gender, urban residency, low education, high blood pressure, body mass index, waist circumference, waist to hip ratio, serum triglyceride and glucose levels were the risk factors for FLD. CONCLUSION: FLD, especially NAFLD, is prevalent in South China. There are many risk factors for FLD.