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Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is a growing problem and the commonest cause of chronic liver disease throughout the world. Given the strong association between NAFLD and insulin resistance and obesity, as well as the central role of ghrelin in these metabolic disorders, we explored whether ghrelin (GHRL) and ghrelin receptor (GHSR) gene polymorphisms were associated with susceptibility to NAFLD. Methods: In this case-control retrospective study which was conducted between April 2010 and July 2013, GHRL (rs696217 or Leu72Met) and GHSR (rs2922126) gene polymorphisms were genotyped in 153 cases with biopsy-proven NAFLD and 157 controls using the polymerase chain reaction - restriction fragment length polymorphism method. Results: The GHRL rs696217 "GT+TT" genotype or "GT" genotype compared with the "GG" genotype occurred less frequently in the patients with NAFLD than the controls and the differences remained significant after adjustment for confounding factors such as age and body mass index (p=0.018; OR=0.35, 95%CI: 0.14-0.84 and p=0.046; OR=0.40, 95%CI: 0.16-0.98, respectively). Furthermore, the GHRL rs696217 'T' allele compared with 'G' allele was significantly underrepresented in the cases (p=0.007; OR=0.33, 95%CI: 0.15-0.76). Nevertheless, no significant difference was found for GHSR rs2922126 gene polymorphism. Conclusions: Our findings suggested, for the first time, that the GHRL rs696217 or Leu72Met "GT+TT" genotype and "GT" genotype compared with "GG" genotype, as well as the "T" or Met72 allele compared with "G" or Leu72 allele had a protective effect for NAFLD susceptibility. However, other studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]