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Introduction The PER2 (Period circadian regulator 2) gene is related to the circadian clock, and it has been deemed as a suppressor gene in osteosarcoma and lung carcinoma. However, the part of PER2 in CRC (colorectal cancer) needs to be further determined. Methods First, we collected clinical samples to detect PER2 expression in CRC. Then, we used cell transfection to knock down PER2 expression in CRC cell lines and performed a series of functional experiments to elucidate the effects of PER2 on CRC cells. We next verified whether PER2 affects the epithelial-mesenchymal transformation (EMT) process in CRC by conducting quantitative real-time PCR and western blotting. Results In the research, we revealed that the expression of PER2 decreased in CRC clinical samples. In addition, knocking down PER2 expression caused CRC cells to acquire malignant biological features. Finally, we found that PER2 knockdown may activate the Snail/Slug axis through inhibiting p53, therefore promote the activation of the EMT pathway. Conclusion In conclusion, low PER2 expression reinforces migration and activates EMT in CRC, suggesting that PER2 is closely related to CRC development and could be used as a potential treatment site in the clinic.