Objective To assess the effectiveness and safety of nedaplatin combined with 5-fluorouracil (5-Fu) for advanced esophageal cancer. Methods Such databases as PubMed, The Cochrane Library, EMbase, CBM, CNKI, VIP and WanFang Data were searched from the date of their establishment to May 4th, 2012 to collect the randomized controlled trials (RCTs) about nedaplatin combined with 5-Fu versus cisplatin combined with 5-Fu for advanced esophageal cancer. According to the inclusion and exclusion criteria, two reviewers independently screened literature, extracted data and assessed the quality of the included studies. Then meta-analysis was conducted using RevMan 5.1 software. Results A total of 15 RCTs invloving 863 patients were included. The results of meta-analysis suggested that, compared with cisplatin combined with 5-Fu, nedaplatin combined with 5-Fu could improve short-term effects (RR=1.31, 95%CI 1.14 to 1.52, P=0.000 2) and reduce gastrointestinal reaction and renal function impairment, but it was associated with aggravated myelosuppression, increase of thrombocytopenia and leukopenia, and decrease of hemoglobin. There were no significant differences between the two groups in liver function impairment, diarrhea and peripheral neurovirulence. Conclusion Nedaplatin combined with 5-fluorouracil can increase short-term effects and reduce gastrointestinal reaction and renal function impairment. However, nedaplatin is associated with aggravated myelosuppression, so it should be applied in clinic with cautious. Nedaplatin combined with 5-fluorouracil can be used as a replacement chemotherapy regimen for advanced esophageal cancer, but the evidence about long-term effects and safety is still required. For the quality and quantity limitation of the included studies which decreases the level of evidence, so the conclusion of this systematic review only provides some references for clinical practice and research.