Objective：To explore the regulatory effect of the enhancer of Zeste homolog 2（EZH2）on the focal adhesion kinase （FAK）/filamentous actin（F-actin）/reactive oxygen species（ROS）pathway，and to analyze its effect on the proliferation，invasion，and metastasis of colorectal cancer（CRC）cells. Methods：Tissue samples from 50 patients undergoing CRC resection at the First Affiliated Hospital of Hebei North University were collected，including both cancer tissues and adjacent normal tissues. Immunohistochemistry was used to detect EZH2 expression，and clinical data were analyzed to determine the correlation between EZH2 expression and clinicopathological parameters as well as survival prognosis. A subcutaneous xenograft model using CRC nude mice was established， dividing the mice into the negative control（EZH2 NC）group，EZH2 overexpression（EZH2 mimic）group，EZH2 NC+cytochalasin D group，and EZH2 mimic+cytochalasin D group. After 14 days of cultivation，the tumor growth was observed. Human CRC cell lines SW480 and SW620 cells were cultured in vitro and divided into the same four groups using lipofection. Western blot was used to detect the expression of FAK，F-actin，and ROS pathway-related proteins. Immunofluorescence staining was used to observe F-actin expression and distribution. Wound healing，transwell，and CCK -8 assays were used to assess cell migration，invasion，and viability. ChIP -qPCR was used to detect the enrichment of FAK，NADPH oxidase（NOX）-2，and NOX4 on EZH2. Results：Immunohistochemistry analysis showed the expression levels of EZH2 were significantly higher in CRC tissues than in adjacent normal tissues（P ＜ 0.05）. EZH2 expression levels were closely associated with lymph node metastasis and distant transfer events（all P ＜ 0.05）. The analysis of follow-up data showed that the 5 - year overall survival rate of CRC patients with low EZH2 expression was significantly higher than that of patients with high EZH2 expression，with a statistically significant difference（P ＜ 0.05）. The subcutaneous CRC xenograft model was successfully established，with the EZH2 mimic group showing significantly larger tumor volumes than that of the EZH2 NC group（P ＜ 0.05）. Post cytochalasin D intervention，both EZH2 NC+cytochalasin D and EZH2 mimic+cytochalasin D groups showed significantly reduced tumor volumes compared with the untreated groups（P ＜ 0.05），though no significant difference was noted between the two intervention groups（P ＞ 0.05）. The expression levels of EZH2，p-FAK，p-Paxillin，NOX2，NOX4，and p-JNK proteins in the EZH2 mimic group were significantly higher than those in the EZH2 NC group（P ＜ 0.05），while the expression levels of RUNX family transcription factor 3（RUNX3）protein were slightly lower than that in the EZH2 NC group（P ＜ 0.05）. The number of F - actin distribution，migration ability，and cell viability increased in the EZH2 mimic group than in the EZH2 NC group. After the intervention of cytochalasin D，there was no significant difference in the expression levels of EZH2，p-FAK，and p-Paxillin proteins compared with the untreated group（P ＞ 0.05），while the expression levels of NOX2，NOX4，and p - JNK proteins were significantly decreased（P ＜ 0.05），and the expression levels of RUNX3 protein were significantly increased compared with the untreated group（P ＜ 0.05）. There was no significant difference between the two intervention groups（P ＞ 0.05）. In addition，the number of F-actin distribution，migration ability，and cell viability were significantly decreased in the intervention groups，with no significant difference between the two groups （P ＞ 0.05）. The results of the ChIP-qPCR assay showed that after using the EZH2 antibody，the promoter contents enriched by FAK， NOX2，and NOX4 were significantly increased，respectively（P ＜ 0.05）. Conclusion：EZH2 promotes the proliferation，invasion，and metastasis of CRC cells by upregulating the activity of the FAK/F-actin/ROS pathway.