Objective: To explore the expression level of serum miR135a-5p and its diagnostic value in colorectal cancer (CRC). Methods: Serum samples were randomly collected from 60 primary CRC patients, 40 patients with intestinal polyps and 50 healthy controls, and the serum concentrations of miR135a-5p, CEA and CA199 were detected. The relationships between serum miR135a-5p level and clinicopathological parameters were analyzed by Mann-Whitney U test. The correlation of serum miR135a-5p level and serum concentrations of CEA or CA199 was analyzed by Pearson's correlation test.Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate the diagnostic efficacy of miR135a-5p, CEA and CA199 as diagnostic indicators. Results: The serum level of miR135a-5p in CRC patient was 2.451 (1.107, 4.413), significantly higher than 0.946 (0.401, 1.942) in the patients with intestinal polyps and 0.949 (0.194, 1.415) in the healthy controls (U = 351.0 and U = 313.0, respectively, P<0.001). The serum level of miR135a-5p in CRC patients was associated with both histological differentiation and clinical stage (P<0.05 for both), however, not correlated with the serum concentration of CEA (r2 = 0.023, P = 0.293) or CA199 (r2 = 0.067, P = 0.068). The AUC of serum miR135a-5p level in CRC patients was 0.832 (0.730-0.930) when compared to the patients with intestinal polyps and was 0.875 (0.800-0.950) when compared with the healthy controls. Conclusions: The serum level of miR135a-5p in CRC patients is significantly higher than that in patients with intestinal polyps and healthy controls, and might be an important diagnostic marker of CRC.