Provided are a small interfering RNA (siRNA) that inhibits the expression of an angiopoietin-like protein 3 (ANGPTL3) gene, and a pharmaceutical composition and a conjugate comprising the siRNA； each nucleotide in the siRNA is independently a modified or unmodified nucleotide, and the siRNA comprises a sense strand and an antisense strand； the sense strand comprises a nucleotide sequence A, the nucleotide sequence A being equal in length to the nucleotide sequence as represented by SEQ ID NO: 1, having a difference of no more than 3 nucleotides； the antisense strand comprises a nucleotide sequence B, the nucleotide sequence B being equal in length to the nucleotide sequence as represented by SEQ ID NO: 2, having a difference of no more than 3 nucleotides.本發明提供一種抑制血管生成素樣蛋白3(ANGPTL3)基因表現的siRNA，含有該siRNA的藥物組合物和綴合物。該siRNA中的每個核苷酸各自獨立地為修飾或未修飾的核苷酸，該siRNA含有正義鏈和反義鏈，該正義鏈含有核苷酸序列A，該核苷酸序列A與SEQ ID NO：1所示的核苷酸序列長度相等，且不多於3個核苷酸差異，該反義鏈含有核苷酸序列B，該核苷酸序列B與SEQ ID NO：2所示的核苷酸序列長度相等，且不多於3個核苷酸差異。本發明提供的siRNA及其藥物組合物和綴合物，可以有效治療和/或預防血脂異常。
