The present cross-sectional study included 150 unrelated non-alcoholic fatty liver disease (NAFLD) patients and 150 healthy subjects. ADIPOQ (-11377C / G) variant was genotyped with polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) method for both patients and controls. Anthropometric and biochemistry parameters were measured. The Homeostasis Model Insulin Resistance Assessment (HOMA-IR) was used to assess the insulin resistance. The rs266729 polymorphism was associated with NAFLD with significant increase in CG genotype compared to those with the wild genotype CC (OR = 9.24, 95% CI = 4.96 - 17.21, p < 0.001) in co dominant tested inheritance model as well in dominant tested inheritance model with CG/GG genotype (OR = 9.58, 95% CI = 5.32 – 17.28, p < 0.001). The G allele increased the risk of NAFLD (OR = 6.06, 95% CI = 3.65 - 10.05, p < 0.001) in comparison with C allele. Subgroup comparison in NAFLD revealed significant higher levels of waist circumference (WHR), HOMA-IR, systolic blood pressure (SBP), fasting glucose and LDL-C in GG and GC carriers compared to CC genotype and significant lower levels of serum adiponectin. The study suggests that ADIPOQ gene polymorphism can be used as a helpful biomarker for NAFLD and abnormal metabolic parameters. Our study sheds light on its role that might be played in the pathogenesis of NAFLD. Proper evaluation of NAFLD is likely to improve therapy effectiveness and safety management.