Objective To investigate efficacy and toxicity of XELOX or FOLFOX4 regimen as neoadjuvant concurrent chemoradiotherapy for stage Ⅱ/Ⅲ middle and low rectal cancer. Methods From June 2011 to March 2014, 120 patients with stage Ⅱ/Ⅲ middle and low rectal cancer who underwent the surgical treatment were enrolled in The Fifth People’s Hospital of Qinghai Province, then were randomly divided into radiotherapy+FOLFOX4 regimen group and radiotherapy+XELOX regimen group. The radiotherapy and chemotherapy were performed simultaneously before the radical resection of rectal cancer. Three-dimensional conformal radiotherapy: 1.8–2.0 Gy/times, 5 times/week, a total of 25 times, the total dose was 45.0–50.0 Gy. At the same time, 2 cycles of chemotherapy were performed according to the FOLFOX4 program (oxaliplatin+leucovorin+5-fluorouracil) or XELOX regimen (capecitabine tablet+oxaliplatin). The radical surgery was performed on 4 to 8 weeks after the preoperative chemoradiotherapy, then 8 to 12 cycles of FOLFOX4 chemotherapy and 4 to 6 cycles of XELOX chemotherapy were completed in the radiotherapy+FOLFOX4 regimen group and the radiotherapy+XELOX regimen group respectively on 1 month after the radical surgery. The curative effect and the occurrence of acute toxicity were observed. Results ① There were no significant differences in thegeneral data such as the gender, age, cT stage, cN stage, TNM stage, histological type, differentiation degree, etc. between the two groups(P>0.05). ② The reduced staging rates of cT and cN in the radiotherapy+XELOX regimen group was 63.3% (38/60) and 86.7% (52/60), respectively, which was significantly higher than that in the radiotherapy+FOLFOX4 regimen group〔38.3% (23/60) and 53.3% (32/60), respectively〕 , the differences were statistically significant (P<0.05). ③ The complete response rate and the effective rate (complete response rate+partial response rate) in the radiotherapy+XELOX regimen group were significantly higher than those in the radiotherapy+FOLFOX4 regimen group (P<0.05). ④ The overall 3-year survival rate in the radiotherapy+XELOX regimen group was significantly higher than that in the radiotherapy+FOLFOX4 regimen group (P<0.05). There were no significant differences in the 3-year disease-free survival rate, distant metastasis rate, and local recurrence rate between the two groups (P>0.05). ⑤ All the patients suffered from 3 to 4 degrees toxicities, however, the incidence rates of the overall toxicity and the diarrhea toxicity in the radiotherapy+XELOX regimen group were significantly lower than those in the radiotherapy+FOLFOX4 regimen group (P<0.05). Conclusion Preliminary results of limited cases in this study show that XELOX regimen is more effective and less acute toxicity than FOLFOX4 regimen for preoperative concurrent chemoradiotherapy for patients with stage Ⅱ/Ⅲ middle and low rectal cancer.