Objective To study the relationship between α-fetoprotein (AFP) polymorphisms and peripheral AFP level in hepatocellular carcinoma (HCC) patients. Methods Using polymerase chain reaction-ligation detection reaction (PCR-LDR) technique, we determined the polymorphisms of AFP of 335 HCC patients; the serum levels of AFP were also determined. SPSS 13.0 software was used for statistical analysis. Results The GG genotype frequency of -205 C>G of AFP gene was significantly different between patients with AFP values ≥20 and <20 ng/mL (GG vs CC: χ²= 4.389, P=0.036). The frequency of G allele was also found significantly different between patients with AFP values ≥400 and <400 ng/mL (G vs C: χ²=4.410, P=0.036). No relationship was found between AFP expression and other polymorphisms, including intron1 A>T, intron7 A>G, 3'UTR A>G and intron2 A>G, in AFP gene. Conclusion In HCC patients among Chinese Han population, the C allele and CC genotype of -205 C>G polymorphism site in AFP gene is associated with higher AFP values.