Objective To explore the effect of down⁃regulation of XRCC6 on apoptosis and invasion of colorectal cancer cells and the changes of ATM/CHK2/p53 signaling pathway. Methods Human colorectal cancer SW620 cells were divided into three groups: control group, si⁃NC group and si⁃XRCC6 group. MTT assay was used to detect cell viability. Flow cytometry was used to detect cell apoptosis. Cell scratch test was used to detect cell migration. Transwell was used to detect cell invasion. qPCR was used to detect ATM, CHK2 and p53 mRNA expression. Western blot was used to detect ATM, CHK2, p53 protein expression and the phosphorylation level of p⁃ATM, p⁃CHK2 and p⁃p53. Results MTT results showed that the cell viability of si⁃XRCC6 group was significantly lower than that of control group and si⁃NC group (P<0.05). Flow cytometry results showed that the survival rate of si⁃XRCC6 group was lower than that of control group and si⁃NC group (P<0.01), the early apoptosis rate was increased (P<0.01), the proportion of late apoptotic cells increased significantly (P<0.01), and there was no significant difference between si⁃NC group and si⁃XRCC6 group (P>0.05).Compared with the control group and si⁃NC group, the migration ability and invasion ability of si⁃XRCC6 group decreased (P<0.01). qPCR and Western blot results showed that the mRNA and protein expression levels of ATM, CHK2 and p53 in si⁃XRCC6 cells increased, and the phosphorylation level of p⁃ATM, p⁃CHK2 and p⁃p53 also increased. Conclusion Down regulation of XRCC6 can inhibit the activity of human colorectal cancer cells and induce early apoptosis, which may be related to the regulation of ATM, CHK2 and p53 signaling pathways and their phosphorylation levels.