The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs havealready been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression andassociation with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptasepolymerasechain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normalmucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a,patients were divided into two groups. The relationship between miR-376a expression and clinicopathologicalfactors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical followupinformation and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC)staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growthfactor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normaltissues and altered high miR-376a expression tended to be positively correlated with advanced lymph nodemetastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients withhigh expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognosticbiomarker and potential therapeutic target in colorectal cancer.