Objective To assess the effectiveness and safety of hyperthermia combined with chemotherapy for advanced colorectal cancer. Methods Databases such as CNKI, VIP, WanFang Data, CBM, EMbase, PubMed and The Cochrane Library (Issue 3, 2012) were electronically searched from the date of their establishment to June, 2012, and the relevant literature and conference proceedings were also manually searched to include randomized controlled trials (RCTs) on comparison of chemotherapy with hyperthermia plus chemotherapy for advanced colorectal cancer. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then the meta-analysis was performed by using RevMan 5.1 software. Results A total of 11 RCTs involving 708 patients with advanced colorectal cancer were included. The results of meta-analysis showed that: a) as for effectiveness, the chemotherapy combined with hyperthermia group was superior to the chemotherapy group in the partial improve rate (OR=1.65, 95%CI 1.39 to 1.97, Plt;0.000 01) and the total effective rate (OR=3.59, 95%CI 2.51 to 5.12, Plt;0.000 01), with significant differences; b) as for safety, the chemotherapy combined with hyperthermia group was lower than the chemotherapy group in the incidence of neurotoxicity (OR=0.50, 95%CI 0.33 to 0.75, P=0.000 8). Conclusion Compared with chemotherapy, chemotherapy combined with hyperthermia can increase partial improve rate and total effective rate and reduce the incidence of neurotoxicity. Due to the limitation of the included studies, large sample size, multicenter, high quality studies are needed to verify the above conclusion. We recommend that chemotherapy combined with hyperthermia therapy could be applied to clinic combining individual conditions of patients.