BACKGROUND: Colorectal cancer (CRC) is the third most common malignant disease around the world. Because the hosts' immunity plays a great part in regulating tumor cells' growth and progression, immunotherapies have therefore aroused great interest in treating cancers. Currently, scientists have investigated the use of Schistosoma-derived soluble egg antigens (SEA), which is known as a strong immune modulator, in treating a series of immune-related diseases. METHODS: In this study, we investigated the anti-tumor effect of SEA against CRC using in vitro cell lines, HCT-116 and DLD-1, as well as in vivo mouse xenograft model. Approaches such as migration assay, invasion assay, and western blotting were done to analyze the anti-tumor effect of SEA. Furthermore, qRT-PCR and ELISA were performed to identify the immune profile of SEA-treated cells as well as SEA-treated xenograft mice. RESULTS: In vitro studies suggested that SEA can dose-dependently inhibit the growth and progression of HCT-116 and DLD-1 cells. This inhibition was accompanied by a reduction of epithelial-mesenchymal transition (EMT), inflammasome inactivation, and apoptosis. SEA also downregulated the expression of IL-4 and IL-10 in the CRC cells, which may be the reason why their growth and progression were suppressed. In vivo studies showed a similar beneficial effect of SEA, as local administration of 25 μg SEA significantly inhibits tumor cell growth. SEA treatment also shifts the host's immunity from a pro-tumorigenic response to an anti-tumor response. CONCLUSION: In conclusion, SEA may provide a beneficial effect against CRC, and further investigation may give promise in CRC treatment.