Objective: To investigate the influence of FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil) regimen plus radiotherapy on the efficacy of surgical treatment of locally advanced colorectal cancer and postoperative recurrence. Methods: The clinical data of 64 patients with locally advanced colorectal cancer treated over the past 3 years were retrospectively analyzed. Of the patients, 30 cases underwent surgical treatment alone (control group), and 34 cases were subjected to preoperative radiotherapy and FOLFOX chemotherapy (observational group). The tumor resection rate, anal preservation rate, postoperative complications, and tumor recurrence between the two groups were compared, and the relationship between the preoperative CEA concentration in patients and their postoperative recurrence were also analyzed. Results: Thirteen patients in control group and 28 patients in observational group had complete tumor excision, and 4 cases in control group and 11 cases in observational group underwent low colorectal anastomosis, respectively, and the differences reached statistical significance (P=0.001 and P=0.034). The incidence of postoperative complications and 3-year cumulative recurrence rate between the two groups showed no statistical difference (P=0.54 and P=0.76), but the 1- and 2-year recurrence rate in observational group were significantly lower than those in control group (P=0.001 and P=0.025). The postoperative CEA level was significantly lower than that before surgery in patients undergoing tumor resection (P<0.01), and there was a negative correlation between preoperative CEA level and time to tumor recurrence (r2=0.26, P=0.0013). Conclusion: Preoperative neoadjuvant therapy can improve tumor resection and anal perseveration rate, and reduce the 2-year recurrence rate in patients with locally advanced colorectal cancer, and not increase the surgical complications; those with high preoperative CEA level are more likely to have an early recurrence.