This systematic review evaluates the clinical evidence for the addition of herbal medicines (HMs) to FOLFOX 4 for advanced colorectal cancer (ACRC) in terms of tumor response rate (tRR), survival, quality of life and reduction in adverse events (AEs). Seven electronic databases were searched for randomized controlled trials (RCTs) of FOLFOX4 combined with HMs compared to FOLFOX4 alone. Outcome data for 13 randomized controlled trials were analysed using Review Manager 5.1. Risk of bias for objective outcomes including tumor response and survival was judged as low. Publication bias was not evident. Meta-analyses found the addition of HMs improved tRR (RR 1.25, 95% CI 1.06-1.47, I-2 = 0%), one year survival (RR 1.51, 95% CI 1.19-1.90, I-2 = 0%) and quality of life in terms of Karnofsky Performance Status (KPS) gained (RR 1.84, 95% CI 1.54-2.19, I-2 = 0%); alleviated grade 3 and 4 chemotherapy-related AEs for neutropenia (RR 0.33, 95% CI 0.18-0.60, I-2 = 0%), nausea and vomiting (RR 0.34, 95% CI 0.17-0.67, I-2 = 0%) and neurotoxicity (RR 0.39, 95% CI 0.15-1.00, I-2 = 0%), compared to FOLFOX4 alone. The most frequently used herbs were Astragalus membranaceus, Panax ginseng, Atractylodes macrocephala, Poria cocos, Coix lachryma-jobi and Sophora flavescens. In experimental studies, each of these herbs has shown actions that could have contributed to improved tumor response. Copyright (C) 2013 John Wiley & Sons, Ltd.