Abstract: Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide, and reducing the mortality rate has become an urgent public health issue. Elucidation of the underlying mechanisms by which gastric cancer evolves from a precancerous lesion to a malignant tumor is important for identifying key targets and blocking disease progression. Recently, important breakthroughs have been made in single-cell RNA transcriptome sequencing (scRNA-seq) technology. scRNA-seq can discriminate cellular heterogeneity and predict and analyze cell-cell interactions, identify novel mutations in cancer cells, explore the progressive epigenomic changes that occur during progression from precancerous to malignant tumors. Therefore, this paper describes the potential mechanisms of gastric cancer malignancy from the perspective of single-cell sequencing, focusing on the epithelial cell state and evolutionary dynamics during "malignant" progression of gastric cancer, the kinetic resolution of cell-cell interactions networks and changes in the TME of both non-malignant and malignant tissues, as well as the application of single-cell transcription in the evolutionary study of gastric cancer.