Hei Yi Zhuang is an isolated subgroup of the Zhuang minority in China. This study was designed to compare the difference in the hepatic lipase gene (LIPC) -514C/T polymorphism and its association with lipid profiles between the Guangxi Hei Yi Zhuang and Han populations. Genotyping of the LIPC -514C/T was performed in 873 subjects of Hei Yi Zhuang and 867 participants of Han Chinese. The frequency of -514T allele was 43.47% in Hei Yi Zhuang, and 36.10% in Han (P < 0.001). The frequencies of CC, CT and TT genotypes were 30.01, 53.04 and 16.95% in Hei Yi Zhuang, and 40.95, 45.91 and 13.14% in Han (P < 0.001); respectively. Serum high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B levels in both ethnic groups were higher in LIPC -514T carriers than in C carriers. In addition, serum triglyceride levels in Han were higher in TT genotype individuals than in CC genotype subjects (P < 0.05). Serum HDL-C levels were positively correlated with age, alcohol consumption and LIPC -514C/T genotypes, and negatively associated with hypertension and cigarette smoking in Hei Yi Zhuang (P < 0.05-0.01), whereas HDL-C levels were positively correlated with age, alcohol consumption and LIPC -514C/T genotypes, and negatively associated with body mass index and cigarette smoking in Han (P < 0.05-0.001). The differences in serum HDL-C levels between the two ethnic groups might partially attribute to the differences in the LIPC -514C/T polymorphism.