Abstract: KRAS is the most frequent mutation subtype of the RAS family, which is the most frequently mutated oncogene in human cancer. Most of the mutations are at codon 12. KRAS causes uncontrolled cell growth after mutation, which in turn leads to the development and progression of cancer diseases. However, despite more than 30 years of effort, the drug discovery targeting RAS constantly fails due to its strong affinity with GTP and picomolar affinity towards guanosine substrates, rendering RAS undruggable. Recently, G12C-specific covalent inhibitors against mutations have made breakthroughs in clinical trials, providing clinical evidence for RAS drug-solvable targets. This review summarizes the structure and function of KRAS and design and clinical research of its small molecule inhibitors, with a focus on the study of recent advances on representative KRAS G12C inhibitors as a new approach to the development of antitumor drugs.