Background: The frequency of MAFLD/NAFLD is surpassing twenty percent and increased in most areas of the world. Egypt is considered among the most 10 countries in predominance of obesity which forms one of the major components of MAFLD. The "multiple hit" concept shows that MAFLD is activated by a combination of several insults acting on susceptible individuals. The PNPLA3 gene is expressed in both adipocytes and hepatocytes and It's an essential factor in controlling the livers lipid metabolism. The PNPLA3 type is communicated in both adipocytes and hepatocytes, and It's fundamental in controlling the liver's lipid metabolism.  Aim: The objective of this research was to study the pattern of PNPLA3 polymorphism C/G (rs738409) among Egyptian MAFLD. Patients Methods: This study included 80 participants with MAFLD and 20 healthy control. Demographic, biochemical, and hematological tests were performed on all participants. The diagnosis of liver steatosis was done by Conventional and Dixon MRI examination of liver. Liver fibrosis was assessed by share wave elastography Detection of PNPLA3 polymorphism C/G (rs738409) in the serum was performed with real-time PCR. Results: The objective of our work was to show the form of PNPLA3 polymorphism C/G (rs738409) among Egyptian MAFLD persons. Methods: We included 80 persons who had MAFLD and 20 healthy controls. We performed Demographic, biochemical, and hematological laboratory investigations on all groups of the study.  We assessed Liver steatosis using Conventional and Dixon MRI examination of liver. We assessed liver fibrosis using share wave elastography. Detection of PNPLA3 polymorphism C/G (rs738409) at the serum was by real-time PCR. Results: The mutant PNPLA3 polymorphism (GG) was higher in 59 MAFLD members (74%) than the controls around 5 members (25%). This finding was detected regardless of presence or absence of diabetes or obesity. (P value < 0.001). Conclusion: The mutation of PNPLA3 plays role in pathogenesis of MAFLD in Egyptian patients.