〔Abstract〕 Objective Based on the expression of NFATc1 and prognosis in colorectal cancer, we interfered NFATc1 via shRNA transfection, analyzed the effect of NFATc1 on colorectal cancer cell proliferation, and further explored potential mechanisms.Methods We explored the correlation between NFATc1 expression and the prognosis of colorectal cancer using the TCGA database.Thereafter, we compared the expression of NFATc1 in colorectal cancer tissues and adjacent normal tissues by immunohistochemical staining of postoperative samples from clinical colorectal cancer patients.We analyzed the effect of NFATc1 on colorectal cancer cell proliferation by measuring CCK-8 after NFATc1 interfered using shRNA transfection; Tumorigenic potential of colorectal cancer cells was measured with clone formation assay; Cell cycle distribution was measured by flow cytometry after propidium iodide staining. The effect of NFATc1 on the transcriptional activity of cell-cycle-related factors was measured by qPCR. Results Based on the TCGA data,we found that high NFATc1 expression in colorectal cancer patients was associated with poor prognosis. The expression of NFATc1 in clinical colorectal cancer tissues was significantly higher than that in adjacent normal tissues. Additionally,interference with NFATc1 inhibited the proliferation rate of colorectal cancer cells in vitro,and the clonogenic capacity of cells was impaired. As expected,the cell cycle was arrested at the G0/G1 phase. The qPCR results indicated that the knockdown of NFATc1 increased the transcriptional activity of multiple key cell cycle inhibitors. Conclusion NFATc1 promotes cell cycle progression by inhibiting the transcriptional activity of cell cycle regulatory factors,thereby promoting the proliferation and tumorigenic ability of colorectal cancer cells.