Background and Aims:Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Previous studies have suggested that TCF7L2 rs7903146 was related to the risk of developing NAFLD but the conclusions are not consistent and no related study has been conducted in Chinese populations. The aim of this study was to investigate the association be-tween TCF7L2 rs7903146 and the risk of developing NAFLD and CAD in a Chinese Han population. Methods: TCF7L2 rs7903146 genotypes were measured by the MALDI-TOF-MS from 143 NAFLD patients, 159 CAD patients, 131 NAFLD+ CAD patients, and 212 healthy controls. The demographic data and serum lipid profiles of all subjects were collected. The distributions of genotype and allele frequency in each group were also tested. Logistic regression was used to inves-tigate the risk of TCF7L2 rs7903146 with NAFLD and CAD. All statistical analyses were conducted using SPSS 23.0. Results: There were no significant differences in the distri-butions of TCF7L2 rs7903146 genotype and allele frequency in each of the two groups, and the TCF7L2 rs7903146 CT+TT genotype did not increase the risk of developing NAFLD, CAD, and NAFLD+CAD. Except for body mass index in the control group, the differences of clinical parameters between the TCF7L2 rs7903146 T allele carriers and non-carriers in each group were not significant. In the non-obese group, the TCF7L2 rs7903146 CT+TT genotype was a protective factor for the development of NAFLD in the non-obese subjects (odds ratio=0.359, 95％ confidence interval: 0.134-0.961, p = 0.041). Conclusions: TCF7L2 rs7903146 was not associated with the risk of developing NAFLD, CAD, and NAFLD + CAD in the Chinese Han population. In the non-obese population, the TCF7L2 rs7903146 CT + TT genotype was a protective factor against the development of NAFLD.