Provided are an siRNA for inhibiting the expression of a hepatitis B virus gene, a pharmaceutical composition and a conjugate comprising the siRNA. Each of the nucleotides in the siRNA is independently a modified or unmodified nucleotide, and the siRNA contains a sense strand and an antisense strand. The sense strand contains a nucleotide sequence A which is equal in length to the nucleotide sequence shown in SEQ ID NO: 1, with no more than 3 nucleotide differences, and the antisense strand contains a nucleotide sequence B which is equal in length to the nucleotide sequence shown in SEQ ID NO: 2, with no more than 3 nucleotide differences.本發明提供一種抑制B型肝炎病毒基因表現的siRNA，含有該siRNA的藥物組合物和綴合物。所述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，所述正義鏈含有核苷酸序列A，所述核苷酸序列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，所述反義鏈含有核苷酸序列B，所述核苷酸序列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具有良好的抑制HBV基因的表現的活性。
