Objective: To determine the efficacy of neoadjuvant chemotherapy combined with three-dimensional (3D) conformal radiation in conversion therapy for unresectable advanced rectal cancer. Methods: Fifty-six patients with unresectable advanced rectal cancer (12 patients with liver metastases) admitted from January 2008 to June 2013 were selected. Of the patients, 30 cases assigned to observational group received neoadjuvant chemotherapy plus 3D conformal radiation therapy, and 26 cases, serving as control group, underwent neoadjuvant chemotherapy and conventional radiation therapy. The conversion rate to resectability, postoperative survival, adverse reactions and incidence of complications after treatment between the two groups of patients were compared. Results: The conversion rate to resectability in observation group was significantly higher than that in control group at 16 weeks of treatment (60.0% vs. 26.9%, P=0.013); both progression-free survival and overall survival in observation group were significantly prolonged compared with control group (P=0.046, P=0.029); the incidence of adverse reactions and short-term complications between the two groups showed no significant difference (all P>0.05). Conclusion: Neoadjuvant chemotherapy combined with 3D conformal radiation therapy can effectively increase the conversion rate to resectability for unresectable rectal cancer, and prolong survival time of the patients without increasing the occurrence of adverse reactions and complications.