Abstract: Objective To investigate the effect of resectional therapy combined with radiofrequency ablation on clinical indicators, safety and prognosis of patients with colorectal liver metastasis, and provide evidence for the clinical application of this therapy. Methods A retrospective analysis of 48 cases of colorectal liver metastasis in our hospital from January, 2011 to December, 2013 was performed. All the patients were divided into observation group (22 cases) and control group (26 cases) according to the treatment methods. The control group underwent eradicative resection for colorectal cancer and liver metastases, while the observation group underwent resection combined with radiofrequency ablation. T-test was used to compare the clinical relevant indicators and the incidence of complications; Kaplan Meier progression-free survival curve and overall survival curve were done, and Log rank test was used to compare the prognosis of patients between the two groups. Results The levels of alanine aminotransferase (ALT) and aspertate aminotransferase (AST) after the treatment in both groups increased obviously, but the levels of the serum albumin (ALB) and cholinesterase (CHE) decreased in different degree. Three days and seven days after the operation, ALT, AST, ALB and CHE in the observation group were improved significantly as compared with the control group. All the above differences were statistically significant (P<0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P>0.05). The progression-free survival rate of the observation group was significantly higher than that in the control group (HR=0.420, 95% CI:0.131-0.971, P=0.025), while the overall survival rate of the observation group was similar to that of the control group (HR=1.623, 95% CI:0.748-3.519, P=0.190), and there was no statistical difference (P>0.05). Conclusion The resectional therapy combined with radiofrequency ablation for colorectal liver metastasis can reduce the damage of cancer to the liver function, although the overall survival rate in patients is no significant difference as compared with surgical excision. So the new treatment option is available for patients who cannot undergo resectional therapy, which has a certain clinical value.