Abstract: Small interfering RNA (siRNA) is a new type of nucleic acid drug that plays its therapeutic roles through the RNA interference (RNAi) mechanism to target and silence the expression of target genes at the post-transcriptional level. As a precise, specific and efficient gene silencing therapy, siRNA has attracted much attention in the field of tumor-targeted therapy. Currently, several anti-tumor siRNA therapies have entered the clinical trial stage. This article summarizes the research progress of siRNA in tumor-targeted therapy in recent years, including the mechanism of action for siRNA, the recent development of anti-tumor siRNA drugs, and the optimization strategies for the in vivo delivery of siRNA drugs, aiming to provide new insights for the development and clinical application of anti-tumor siRNA drugs.