Objective: To explore the efficacy and safety of consolidation chemotherapy during neoadjuvant chemoradiation interval in the treatment of mid-low locally advanced rectal cancer. Methods: The clinical data of 64 cases of locally advanced rectal cancer treated in the Second Affiliated Hospital of Guangxi University of Science and Technology from January 2015 to September 2017 were retrospectively analyzed. According to different neoadjuvant treatments, the patients were divided into a non-consolidation chemotherapy group and a consolidation chemotherapy group, with 32 cases in each group. The non-consolidation chemotherapy group received surgical treatment 6–8 weeks after neoadjuvant chemoradiotherapy. The consolidation chemotherapy group received oxaliplatin and capecitabine consolidation chemotherapy during neoadjuvant chemoradiation interval and total mesorectal excision (TME) surgery was performed after 2 weeks. The curative effect, radical resection rate and adverse reactions of chemotherapy were compared between the 2 groups. The expression levels of serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen-199 (CA199)], invasion genes [matrix metalloproteinase-9 (MMP-9), MMP-11 and zinc finger transcription factor (Slug)] before and after the treatment, and the overall survival (OS) rate and disease-free survival (DFS) rate at 3 years were detected and compared. Results: After neoadjuvant therapy, two patients (6.25%) in the non-consolidated chemotherapy group were evaluated as clinical complete remission (cCR), and five patients (15.62%) in the consolidated chemotherapy group were evaluated as cCR, and all were confirmed as pathological complete remission (pCR) by postoperative pathology, there was no significant difference between the 2 groups (P>0.05); the tumor regression classification (TRG) in the consolidation chemotherapy group was better than that in the non-consolidation chemotherapy group (P<0.05). R0 resection rate of the consolidation chemotherapy group was higher than that of the non-consolidation chemotherapy group (P<0.05); the levels of CEA and CA199 in the consolidation chemotherapy group were lower than those in the non-consolidation chemotherapy group (P<0.05). The mRNA levels of MMP-9, MMP-11 and Slug in the surgical resection lesions in the consolidation chemotherapy group were lower than those in the non-consolidation chemotherapy group (P<0.05); the adverse reactions of nausea, vomiting, diarrhea and hematological toxicity in the consolidation chemotherapy group were higher than those in the non-consolidation chemotherapy group (P<0.05). There was no significant difference in the incidence of surgical complications between the 2 groups (P>0.05). The 3-year DFS rate of the consolidation chemotherapy group was 46.88%, which was significantly better than that of the non-consolidation chemotherapy group (34.38%, P<0.05). There was no significant difference in 3-year OS rate between the 2 groups (59.38% vs 53.13%, P>0.05). Conclusion: Consolidated chemotherapy during the interval of neoadjuvant chemoradiotherapy in the treatment of mid-low locally advanced rectal cancer can improve the preoperative treatment effect, increase the resection rate of R0, reduce the level of serum tumor markers, inhibit the invasion of cancer cells, and improve DFS rate.