Background: Circular RNAs (circRNAs) are involved in the growth of many tumors. However, the expression and possible role of circ_cse1l (hsa_circ_0060745) in colorectal cancer (CRC) are unclear. The present study was designed to explore the role of circ_cse1l in CRC. Material/Methods: The levels of circ_cse1l expression in cancer tissues and serum samples of 50 patients with CRC and in con trol subjects were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). CCK-8, colony formation, transwell and wound healing assays were performed to assess the functions of circ_cse1l in CRC cell lines after overexpression. The relationship between circ_cse1l and eIF4A3 during cell proliferation was analyzed by western blotting and RNA-binding protein immunoprecipitation (RIP). Results: qRT-PCR assays showed that the levels of expression of circ_cse1l were lower in CRC cell lines and in tissue and serum samples from patients with CRC than in control samples. The expression of circ_cse1l in CRC tissues had clinical significance, as its level of expression was inversely associated with the depth of tumor invasion. Overexpression of circ_cse1l in HT29 and HCT116 cells markedly reduced cell proliferation and metastasis. Western blotting showed that circ_cse1l overexpression dowregulated the expression of PCNA protein. RIP results demonstrated that circ_cse1l inhibited the proliferation of CRC cells by binding to eIF4A3. Conclusions: The expression of circ_cse1l is downregulated in CRC Furthermore, circ_cse1l downregulated PCNA expression by binding to eIF4A3, inhibiting the proliferation of CRC cells.