Objective. Rab27b is reported to correlate with cancer development and progression. However, the association between Rab27b expression and the clinical characteristics of colorectal cancer (CRC) is barely investigated. Methods. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) test with 18 fresh-frozen CRC samples and immunohistochemistry (IHC) analysis in 113 CRC cases were performed to explore the relationship between Rab27b expression and the clinicopathological features of CRC. Cox regression and Kaplan-Meier survival analyses were executed to evaluate the prognosis of CRC. Results. The results demonstrated that the expression levels of Rab27b mRNA and protein were significantly higher in CRC tissues than that in matched noncancerous tissues (P < 0.05). Rab27b protein expression in CRC was statistically correlated with serum CEA level (P = 0.004), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), and TNM stage (P = 0.001). Cox multifactor analysis and Kaplan-Meier method suggested that higher Rab27b protein expression (P = 0.041) and tumor differentiation (P = 0.001) were significantly associated with the overall survival of CRC patients. Conclusions. The data indicated that higher expression of Rab27b was observed in CRC tissues and Rab27b may be identified as a useful predictor of metastasis and prognosis for CRC.