Abstract: Mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS) are closely associated with the occurrence and progression of tumors. The KRAS protein encoded by it was once considered an “undruggable target”. In recent years, significant breakthroughs have been made in inhibitors targeting the KRAS^G12C mutant, with several drugs being successively approved for marketing, which not only verifies the feasibility of targeting KRAS but also promotes extensive exploration of selective inhibitors against other mutations beyond KRAS^G12C and pan-KRAS inhibitors. With the diversified development of targeting strategies, the application of active small molecules based on novel “drug-target” interaction modes such as proteolysis-targeting chimera and molecular glues in the regulation of KRAS function has also been reported successively. This article reviews the research progress of small-molecule anti-tumor drugs targeting KRAS in recent years, aiming to provide some reference for the drug development of undruggable targets and tumor treatment.