The role of Ras-related protein Rab23 in tumors has attracted increasing attention in recent years; however, whether it can function as an oncogenic protein remains under debate, and its role in colorectal cancer (CRC) is currently unknown. In the present study, high expression of Rab23 in CRC tissues was confirmed using immunohistochemistry, and high expression of Rab23 in CRC cells (SW1116 and HT29) was confirmed using reverse transcription-polymerase chain reaction and western blot analysis. A positive association of Rab23 with tumor size and advanced clinical stage was confirmed by χ
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analysis. In addition, the positive association of Rab23 with poor disease-free survival was confirmed by survival analysis. Cell experiments further demonstrated that overexpression of Rab23 increased the expression of the proliferation marker Ki-67 and the proliferative ability in SW1116 and HT29 cells. Molecular mechanism research revealed that the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) signaling pathways contributed to the high expression of Ki-67 and increased the proliferative ability induced by Rab23 in CRC cells. In conclusion, the study confirmed the high expression of Rab23 in CRC, and its positive association with CRC progression and poor prognosis. Furthermore, the data demonstrated that Rab23 increased the proliferation of CRC cells via the ERK and AKT signaling pathways. These results suggest that Rab23 may be used as a protein for diagnosis and prognosis prediction in patients with CRC, and is proposed to be a novel therapeutic target for improving the patient outcome.