Objective To explore the expression and prognostic significance of UCH37 in colorectal cancer (CRC). Methods Expressions of UCH37 at both mRNA and protein levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Immunohistochemistry in 77 CRC patients. Spearman’s rank test, K-M survival curves and Cox proportional hazards risk were conducted to determine the clinical relevance of UCH37 in CRC. Results QRT-PCR and Immunohistochemistry results revealed that expression of UCH37 was upregulated in CRC tissues compared with adjacent normal tissues, and positive rates of UCH37 in CRC patients at TNM Ⅲ and TNM Ⅳ were increased when compared with that in CRC patients at TNM I and TNM II (P < 0.05). Spearman rank correlation showed that expression of UCH37 was closely associated with lymph node metastasis and venous invasion (P < 0.05). Kaplan-Meier curves suggested that expression of UCH37 was negatively correlated with 5-year overall and progression-free survival time (P < 0.05). Cox proportional hazards risk analysis revealed that UCH37 was an independent prognostic factor for CRC [H^R= 4.998, (95%CI: 1.897, 8.438), P = 0.017]. Conclusions UCH37 is potentially a prognostic biomarker in CRC.