In this study we investigated the effect of poly (ADP-ribose) glycohydrolase (PARG) deficiency on the ability of invasion in CT26 murine colon carcinoma cell and its possible mechanism. We examined the effects of PARG protein knockdown by RNA interference on invasion, migration, and matrix adhesion of colon carcinoma CT26 cell line in vitro and using a murine model of liver metastasis in vivo to observe the average survival time. The expression of integrin-β1, matrix metalloproteinases-9 (MMP-9) and matrix metalloproteinases-2 (MMP-2) was detected by western blot. The activities of MMP-9 and MMP-2 in various group supernatants were measured by zymography. We observed that PARG silencing caused a significant decrease in the number of CT26 cells that adhered to fibronectin (P < 0.5) and invaded to the lower surface of the membrane (P < 0.5). The expression of integrin-β1, MMP-9, and matrix MMP-2 in CT26 cells of the PARG-shRNA group was lower than that of two control groups (P < 0.5). Similar results were observed in the activities of MMP-9 and MMP-2 in various group supernatants (P < 0.5). The average survival time of BALB/c mice with spleen-transplanted PARG-shRNA CT26 tumors was longer compared with control groups (P < 0.05). To conclude, PARG silencing can inhibit the adhesive and invasive abilities of CT26 cells and delay liver metastasis in a mouse model, which might be useful for therapeutic purposes in CRC patients with distant metastasis.