DNA binding protein A (dbpA) belongs to the Y-box binding protein family and has been reported to play an important role in carcinogenesis. Our previous study demonstrated that the knockdown of dbpA in gastric cancer cells inhibited cell proliferation by modulating the cell cycle. However, the role of dbpA in human colorectal cancer (CRC) remains unclear. In this study, immunohistochemical (IHC) staining and clinicopathological parameter analysis were employed to detect dbpA expression in 44 paired CRC samples and 7 CRC cell lines. Lentivirus-mediated short hairpin RNA (shRNA) was used to silence dbpA, and the effects of dbpA knockdown on cell proliferation were determined by MTT assay, colony formation assay and flow cytometry. Furthermore, a xenograft model was established to observe tumor growth in vivo. Functional analysis indicated that dbpA was overexpressed in the CRC tissues and cell lines, and a high dbpA expression was associated with the depth of invasion (p<0.001), the degree of differentiation (p<0.001), lymphatic metastasis (p<0.001) and vessel invasion (p<0.001). The suppression of dbpA expression resulted in decreased cell proliferation in vitro and tumor growth in vivo, and it induced cell cycle arrest and promoted the apoptosis of the CRC cells. As a whole, our findings illustrate the crucial role of dbpA in colorectal tumorigenesis. Thus, dbpA may be used as a novel and potent therapeutic target in CRC.