Background Although genetic features vary across ethnicities, few genome-wide association studies (GWAS) have reported the genetic determinants of liver enzyme expression. This study was aimed to evaluate the associations of genome-wide single nuclear polymorphisms (SNPs) with the liver enzymes in a Korean population. Methods We performed a GWAS to identify genetic loci influencing liver function, as measured by concentrations of alkaline phosphatase (ALP), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) in in Korean study participants. Results A total of 6,488 subjects (4,457 in the discovery and 2,031 in the validation set) were included. The mean subject age was 50.0±10.6 years (male, 53.7%). Among a total of 546,738 SNPs tested, rs651007 and rs579459 located in the ABO gene showed strong associations with ALP (P = 1.63×10−8 and 5.61×10−8, respectively [discovery set]; P = 4.08×10−15 and 9.92×10−16, respectively [validation set]). Additionally, rs5751901 and rs2006092, which are located in the GGT1 gene, showed strong associations with GGT (P = 6.44×10−15 and 1.26×10−15, respectively [discovery set]; P = 4.13×10−10 and 5.15×10−11, respectively [validation set]). Among the 13 SNPs that showed genome-wide significance with total bilirubin levels, rs10929302 and rs6742078 showed the most significant association (P = 3.08×10−64 and 2.05×10−62, respectively [discovery set]; P = 1.33×10−116 and 2.24×10−118, respectively [validation set]). No genome-wide significant associations was found for ALT. Conclusions We demonstrated that ABO, GGT1 and UGT1A family were associated with ALP, GGT and BIL, respectively in Korean population. These findings differ from reported results in GWAS in European populations in terms of associated genes and locations, suggesting different genetic mechanisms of liver enzyme regulation according to ethnicity.