The lower expression of MEG3 was remarkably correlated with low histological grade, deep tumor invasion, and advanced tumor node metastasis (TNM) stage. Multivariate analyses revealed that MEG3 expression served as an independent predictor for overall survival. Further experiments revealed that overexpressed MEG3 significantly inhibited CRC cell proliferation both in vitro and in vivo. MEG3 is involved in the development and progression of colorectal cancer by regulating cell proliferation and shows that MEG3 may be a potential diagnostic and prognostic target in patients with colorectal cancer.