Genome-wide association studies (GWAS) have identified a number of common variants associated with serum liver enzyme homeostasis in population. In the previous study, single nucleotide polymorphisms (SNPs) in several genes have been reported to be associated with serum liver enzyme levels in European population. We aimed to confirm whether the genetic variation of SMAD2 (SMAD family member 2) gene influence the serum liver enzyme levels in Korean population. We genotyped variants in or near SMAD2 in a population-based sample including 994 unrelated Korean adult. Here, we performed association analysis to elucidate the possible relations of genetic polymorphisms in SMAD2 gene with serum liver enzyme levels. By examining genotype data of a total of 944 subjects in 5 hospital health promotion center, we discovered the SMAD2 gene polymorphisms are associated with serum liver enzyme levels. The common and highest significant polymorphism was rs17736760 (${eta}$=3.51, P=5.31E-07) with glutamic oxaloacetic transferase (GOT), rs17736760 (${eta}$=5.99, P=1.25E-05) with glutamic pyruvate transaminase (GPT), and rs17736760 (${eta}$=15.68, P=9.93E-07) with gamma glutamyl transferase (GGT) in all group. Furthermore, the SNP rs17736760 was consistently associated with GOT (${eta}$=5.25, P=1.72E-06), GPT (${eta}$=9.97, P=1.16E-05), GGT (${eta}$=26.13, P=3.43E-06) in men group. Consequently, we found statistically significant SNP in SMAD2 gene that are associated with serum levels of GOT, GPT, and GGT. In addition, these results suggest that the individuals with the minor alleles of the SNP in the SMAD2 gene may be more elevated serum liver enzyme levels in the Korean population.