Abstract: The continuous development of high-throughput and single-cell sequencing technologies and the emergence of spatial transcriptome sequencing have allowed the continuous discovery of temporal and spatial molecular events in the progression of colorectal cancer (CRC) to better understand its mechanism of malignant progression. Genetic variations (mutation of APC and P53, etc.) and mismatch repair of DNA, posttranscriptional regulation, such as epigenetic alteration, and dynamic alteration of complex molecular networks have their own special molecules that play key roles. Drug resistance and metastasis in the late stage of CRC progression are closely related to these key molecular events. This article reviews the research progress and explores key molecular events in the malignant progression of CRC to provide scientific basis and ideas for elucidating the regulatory mechanism of CRC and evaluating its prognosis prediction and treatment.