Abstract: Objective To investigate the role of the -250G/A polymorphism in the promoter region of hepatic lipase gene (LIPC) on serum lipid profile and its interactions with a high-carbohydrate/low-fat (HC/LF) diet on serum lipid profiles in a young healthy Chinese population. Methods After a stabilization diet for seven days, fifty-six young healthy subjects (27 mdles, 29 females) were given the HC/LF diet for six days. The serum lipid profiles were analyzed of the twelve-hour fasting venous blood samples collected in the mornings of the first, the eighth and the fourteenth days. The concentrations of serum apolipoproteins were measured. The LIPC -250G/A polymorphism were analyzed. Results At baseline, the female subjects with the GG genotype had significantly higher high-density lipoprotein cholesterol (HDL-C) (P=0.041) and apolipoprotein A-Ⅰ (Apo A-Ⅰ) (P=0.020) than the male subjects with the same genotype. After the stabilization diet, the females had significantly higher HDL-C (GG genotype:P=0.021, A carriers:P=0.014) and Apo A-Ⅰ (GG genotype:P=0.035, A carriers:P=0.006) than the males in all genotypes. After the HC/LF diet, the female A carriers had significantly higher total cholesterol (TC) (P=0.042) than the male A carriers, and the females had significantly higher Apo A-Ⅰ than the males in all genotypes (GG genotype:P=0.010, A carriers:P=0.009). Compared with those before the HC/LF diet, TC (males with GG genotype:P=0.013, male A carriers:P=0.000; females with GG genotype:P=0.025, female A carriers:P=0.048) and low-density lipoprotein cholesterol (LDL-C) (males with GG genotype:P=0.028, male A carriers:P=0.000; females with GG genotype:P=0.004, female A carriers:P=0.001) significantly decreased after the diet in all the subjects. Triglycerides (TAG) (GG genotype:P=0.006, A carriers:P=0.001) significantly increased in the females regardless of the genotype. However, only in the male A carriers, HDL-C (P=0.011) and Apo A-Ⅰ (P=0.041) significantly increased after the diet. Conclusion The A allele at the LIPC -250G/A polymorphism is associated with the HC/LF diet induced HDL-C and Apo A-Ⅰ concentration changes in the males.