In our previous study, we have found that PLCE1 was down-regulated in sporadic colorectal cancer. But the role of PLCE1 in the incidence of colorectal cancer is still not definite. Therefore, in order to validate whether PLCE1 displays a suppressive role, in this study, we examined the expression of PLCE1 in sporadic colorectal cancer with a larger sample size and the effect of PLCE1 overexpression on cancer cell malignant degree. The expression level of PLCE1 in 50 colorectal cancers with their pair-matched normal tissues was measured by RT-PCR, Western blot, and immunohistochemistry. The effect of PLCE1 overexpression on cancer cell malignant degree was measured by MTT assay, plate colony formation assay, soft agar colony formation assay, cell cycle and apoptosis analysis, and xenograft assay. We found that PLCE1 was down-regulated in 42% (21/50) of colorectal cancer tissues compared with pair-matched normal tissues, more frequent in the poor differentiation tumor in patients under 60. Overexpression of PLCE1 significantly inhibited the proliferation of colon cancer cells and degraded its malignant degree. These results suggest that PLCE1 may be involved in the development of sporadic colorectal cancer through its inhibitory effect on cell proliferation. PLCE1 exhibits a suppressive role in incidence of colorectal cancer.