The objective of the study was to investigate the role of hcrcn81 gene in Wnt/β-catenin signaling pathway related to human colorectal cancer. A total of 30 pairs of human colorectal cancer tissues with control normal tissues were analyzed by qRT-PCR. The proliferation, apoptosis, cell cycle, cell colony and metastasis of LS174T−hcrcn81, HCT116−hcrcn81, LoVo+hcrcn81 and SMMC-7721+hcrcn81 cells were tested, of which hcrcn81 was knockdown in LS174T, HCT116 cells and hcrcn81 was overexpressed in LoVo, SMMC-7721 cells. Besides, the mRNA and protein levels of hcrcn81, β-catenin, c-Myc, cyclinD1, GSK-3β and survivin in colon cancer cell lines were evaluated by qRT-PCR and western blot. The mRNA levels of β-catenin and Survivin were up-regulated in 76.7 % (23/30) and 63.3 % (19/30) of the tumor samples, respectively. hcrcn81 and GSK-3β mRNA expression levels were down-regulated in 20/30 (66.7 %) and 21/30 (70.0 %) of the tumor samples as compared to the adjacent normal tissues, respectively. Furthermore, in LoVo+hcrcn81 and SMMC-7721+hcrcn81 cells, the mRNA and protein levels of β-catenin, c-Myc, cyclinD1 and Survivin were up-regulated, whereas those of GSK-3 were down-regulated. In LS174T−hcrcn81 and HCT116−hcrcn81 cells, the mRNA levels of β-catenin, c-Myc, cyclinD1 and Survivin were down-regulated, whereas GSK-3βmRNA was up-regulated. Cell proliferation in LoVo+hcrcn81 and SMMC-7721+hcrcn81 groups was significantly enhanced (P < 0.05). Proliferation index in both LoVo+hcrcn81 and SMMC-7721+hcrcn81 groups was significantly higher than that in the control groups (P < 0.05). The number of colony in LoVo+hcrcn81 and SMMC-7721+hcrcn81 cells were significantly higher than that in the control groups (P < 0.05). In addition, the percentage of apoptotic cells in LoVo+hcrcn81 and SMMC-7721+hcrcn81 groups were significantly lower than that in the control groups (P < 0.01, P < 0.01). Finally, the number of migrating cells was significantly higher in LoVo+hcrcn81 and SMMC-7721+hcrcn81 groups than that in the control group (P < 0.05). hcrcn81 might promote carcinogenesis and progression through regulation of the Wnt/β-catenin signaling pathway and plays an important role in the carcinogenesis of colorectal cancer.