Objective To explore the relationship between nonalcoholic fatty liver (NFALD)and apolipoprotein E (ApoE)gene polymorphism in Shanghai undergraduate students. Methods A cross-sectional survey was performed in 4 148 students from Shanghai Tongji University. Quesgionary, physical measurement, ultrasonography and biochemical parameters were used to diagnose NFALD. In patients with NAFLD and 200 healthy subjects (served as control), ApoE genotypes were determined by PCR-RFLP. Results (1)Totally 398 subjects were diagnosed as NAFLD (prevalence 9.6%). Body mass index, waist-to-hip ratio, triglycerides, total cholesterol, alanine transaminase, aspartate aminotransferase and γ-glutamyltransferase in NAFLD group were higher than those in control, which were related to the degree of NAFLD (P<0.01). (2)ApoE genotypes distributions were significantly different between two groups (χ2=10.52, P<0.01). In NAFLD,E4/4 genotype frequency (5.5%)increased, and E3/3 (61.8%)decreased . (3)Unconditional logistic regression showed that E4/4 were closely associated with lipid profiles. Conclusion ApoE point mutations 112 and 158 may cause different dyslipidosis. E4/4 genotype seems to be one of the genetic predisposition factors of NAFLD.