To the best of our knowledge, our current study is the first to investigate the association of PNPLA3 rs738409 C>G, TM6SF2 rs58542926 C>T, HSD17B13 rs9992651 G>A, and GCKR rs1260326 T>C SNPs with clinical characteristics, the presence and severity of hepatic steatosis, and liver fibrosis in MASLD in the Egyptian population. This evidence concerns the gene PNPLA3 and fatty liver disease.