Provided are a siRNA for suppressing hepatitis B virus gene expression, and a pharmaceutical composition and conjugate containing the siRNA. Each nucleotide in the siRNA is an independent modified nucleotide. The siRNA contains a positive-sense strand and an antisense strand. The positive-sense strand of the siRNA contains a nucleotide sequence 1 having an equal length to a nucleotide sequence shown in SEQ ID NO: 155 with no more than three nucleotide differences, and the antisense strand of the siRNA contains a nucleotide sequence 2 having an equal length to a nucleotide sequence shown in SEQ ID NO: 156 with no more than three nucleotide differences.本發明提供了一種抑制B型肝炎病毒基因表達的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1，所述核苷酸序列1與SEQ ID NO: 155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2，所述核苷酸序列2與SEQ ID NO: 156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B型肝炎。
