Background: The cisplatin (CDDP)-based CT is considered as the standard regimen for the treatment of moderate to advanced SCCHN. Recently, an alteration is made to carboplatin (CBDCA) because of its similar mode of action. We conducted a meta-analysis to compare the efficacies and toxicities of these two treatments. Methods: The search strategy included Pubmed, Science Direct, the Cochrane Library, China National Knowledge Internet Web. Statistical analyses were performed using RevMan 5.2. The primary endpoint was overall survival (OS) with secondary endpoints of locoregional control (LRC) and severe toxicity (grade ≥ 3). Hazard ratio (HR) and risk ratio (RR) were calculated using random- or fixed-effect models. Kaplan-Meier curves were read by Engauge-Digitizer. Results: Overall 12 studies and 1165 patients were included. CDDP-based CT significantly improved 5-year OS (HR = 0.67,95%CI 0.49-0.91;P = 0.01) compared to the CBDCA group. No difference in 3-year OS/LRC was observed (P = 0.08;P = 0.64), but a subgroup analysis showed a better 3-year OS in the CDDP arm for non-nasopharynx carcinoma (non-NPC) SCCHN (HR = 0.66,95%CI 0.48-0.91;P = 0.01). The CDDP-based CT was associated with more gastrointestinal toxicities (RR = 4.58,95%CI 1.57-13.37;P = 0.005) and nephrotoxicity (4/110 = 3.6%) compared to the CBDCA group, but less hematologic toxicities (anemia, leukopenia and thrombocytopenia) with RRs of 0.27 (95%CI 0.12-0.63),0.71 (95%CI 0.52-0.96),0.28 (95%CI 0.15-0.54). Risk of skin toxicity was identical. Moreover, we found that for non-NPC SCCHN, mucositis occurred more frequently and severely in CDDP-based treatment (RR = 3.55,95%CI 1.42-8.88;P = 0.007), whereas less for NPC (RR = 0.20,95%CI 0.09-0.45;P < 0.0001). Conclusions: Patients with CDDP-based CT can achieve a higher OS, but there is no significant difference in LRC. The CDDP-based CT is associated with less hematologic toxicities but more gastrointestinal toxicities and nephrotoxicity compared to the CBDCA arm. Risk of mucositis in the CDDP group is higher for non-NPC SCCHN, but lower for NPC. The precise roles of CDDP and CBDCA in the management of SCCHN remain to be determined.