The present invention relates to RNAi agents,e.g., double stranded RNAi agents, targeting the Patatin-Like Phospholipase Domain Containing 3 (PNPLA3) gene, and methods of using such RNAi agents to inhibit expression of a PNPLA3 gene and methods of treating subjects having Nonalcoholic Fatty Liver Disease (NAFLD) and/or a PNPLA3-associated disorder.本發明係有關一種靶向含類馬鈴薯儲藏蛋白磷脂酶域3(PNPLA3)基因之RNAi劑,例如,雙股RNAi劑,及使用此等RNAi劑於抑制PNPLA3基因表現之方法,及治療患有非酒精性脂肪肝疾病(NAFLD)與/或PNPLA3-相關病變之個體之方法。