The anti-colorectal cancer activity and underlying mechanisms of SMP-3, both alone and in combination with regorafenib (REG), were evaluated in vitro using HCT116 colorectal cancer cells and normal FHC cells through cytotoxicity, Western blot, and immunofluorescence analyses.<h4>Results</h4>The purified SMP-3 exhibited a total polysaccharide content of 96.52% with a weight-average molecular weight of 61.3 kDa. This evidence concerns the gene PIGZ and colorectal cancer.