The co-stimulatory molecule CD28 plays an important role in T-cell-mediated immune response like acute cellular liver transplant rejection. The aim of the retrospective case- control study was to examine whether the single nucleotide polymorphisms (SNPs) rs3116487, rs3116494, and rs3116496 of the CD28 gene are associated with acute cellular liver transplant rejection. The mentioned SNPs were genotyped in 147 liver transplant recipients without acute cellular rejection and 144 liver transplant recipients with acute cellular rejection by real-time endpoint genotyping. The genotype and allele frequencies of the SNPs did not show any significant differences between both groups. Haplotype analyzes of the SNPs also showed no association. Our data suggest that the analyzed SNPs are not major contributors to the susceptibility of acute cellular liver transplant rejection.