Stanniocalcin 2 (STC2), a secretory glycoprotein hormone, regulates many biological processes including cell proliferation, apoptosis, tumorigenesis and atherosclerosis. However, the effect of STC2 on proliferation, migration and epithelial‑mesenchymal transition (EMT) progression in human colorectal cancer (CRC) cells remains poorly understood. The expression level of STC2 was determined by quantitative real‑time polymerase chain reaction (qPCR) and western blot analysis. Cell Counting Kit‑8 (CCK‑8) was used to detect the viability of SW480 cells. The invasion and migration of cells were identified by wound healing and Transwell assays. The mRNA and protein expression levels of β‑catenin, matrix metalloproteinase (MMP)‑2, MMP‑9, E‑cadherin and vimentin were assessed by qPCR and western blot analysis. In the present study, it was demonstrated that STC2 was highly expressed in the CRC cell lines. After silencing of STC2, the cell viability, migration and invasion were significantly reduced. Silencing of STC2 in the CRC Sw480 cells increased the expression of E‑cadherin and decreased the expression of vimentin, MMP‑2 and MMP‑9, compared to those in the normal and empty vector group. Furthermore, the expression of β‑catenin in the STC2 gene silenced group was suppressed, and the expression of β‑catenin was reversed by Wnt activator, SB216763. These results demonstrated that STC2 participates in the development and progression of CRC by promoting CRC cell proliferation, survival and migration and activating the Wnt/β‑catenin signaling pathway.