Background: Leptin (LEP ) and LEP receptor (LEPR ) polymorphisms may be associated with the development of cancer. 
Methods: In this study, we selected five functional LEP  and LEPR  single-nucleotide polymorphisms (SNPs) and conducted a case–control study to determine the relationship of LEP  and LEPR  polymorphisms with hepatocellular carcinoma (HCC) risk in Eastern Chinese Han population. There were 584 HCC cases and 923 cancer-free controls included in our study. HCC patients and controls were fully matched by age and sex. SNPscan™ genotyping method was used to analyze the genotyping of LEP  rs2167270 G>A, rs7799039 A>G, LEPR  rs6588147 G>A, rs1137100 G>A, and rs1137101 G>A SNPs. 
Results: We found that LEP  rs7799039 A>G and rs2167270 G>A polymorphisms were associated with the susceptibility of HCC in this population (LEP  rs7799039 A>G: GG vs AA: adjusted odds ratio [OR]=2.03, 95% CI, 1.22–3.38, P =0.006 and GG vs AA/AG: adjusted OR=1.97, 95% CI, 1.20–3.22, P =0.007; rs2167270 G.A: AA vs GG: adjusted OR=2.03, 95% CI, 1.10–3.75, P =0.024 and AA vs GG/GA: adjusted OR=2.01, 95% CI, 1.10–3.68, P =0.023). However, LEPR  rs6588147 G>A polymorphism decreased the risk of HCC (GA vs GG: adjusted OR=0.62, 95% CI, 0.45–0.86, P =0.005 and AA/GA vs GG: adjusted OR=0.64, 95% CI, 0.47–0.88, P =0.007). 
Conclusion: This case–control study highlights that LEP  rs7799039 A>G and rs2167270 G>A polymorphisms increase the susceptibility to HCC; however, LEPR  rs6588147 G>A polymorphism may be a protective factor for HCC in Eastern Chinese Han population.
Keywords: LEP, LEPR, polymorphism, hepatocellular carcinoma, risk, single nucleotide polymorphism, hepatitis B virus