Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of a history of alcohol use and with a prevalence of 15%-45% in developed nations. Nonalcoholic steatohepatitis (NASH) is an advanced stage of NAFLD with a pronounced major inflammatory component. The aim of this study was to investigate the possible role of nicotinamide-N-methyltransferase (NNMT) gene rs694539 variant in the development of NASH. Therefore, we analyzed 80 NASH patients and 183 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism method developed in our laboratory. The NNMT rs694539 variant was found to be significantly associated with NASH (χ(2)=9.349, p=0.009). The individuals with the GG genotype had protection against NASH (χ(2)=3.793, p=0.051, odds ratio [OR]=0.580, 95% confidence interval [CI]=0.334-1.006), whereas the individuals with the AA genotype showed statistically significant increased risk for NASH (χ(2)=7.748, p=0.005, OR=7.338, 95% CI=1.448-37.190). Moreover, the G allele was protective against NASH (χ(2)=7.748, p=0.005, OR=0.136, and 95% CI=0.027-0.691). On the other hand, the A allele was a risk factor for NASH (χ(2)=3.793, p=0.051, OR=1.725, and 95% CI=0.994-2.996). Consequently, the rs694539 variant of NNMT gene is a genetic risk factor for developing NASH.