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AIMS This study aimed to prepare and evaluate the physicochemical and anticancer properties of cisplatin and curcumin-loaded mesoporous silica nanoparticles (Cis-Cur-MSNs). BACKGROUND In recent years, combination treatment has attained better outcomes than monotherapy in oncology. Cis-Cur-MSNs were prepared by precipitation technique. OBJECTIVE The objective of the present study was the evaluation of the physicochemical and anticancer properties of cisplatin and curcumin-loaded mesoporous silica nanoparticles (Cis-Cur-MSNs). METHODS The prepared materials were assessed in terms of physicochemical methods. The drug release pattern from the MSNs was also evaluated via ultraviolet spectrophotometry. In addition, the porosity and surface area of prepared nanoparticles were determined using the Brunauer-Emmett-Teller (BET) technique. The cytotoxicity of Cis-Cur-MSNs was evaluated on the HN5 cells as head and neck squamous carcinoma cell lines. Furthermore, ROS production of Cis-Cur-MSNs treated cells was evaluated compared with untreated cells. RESULTS According to the results, prepared nanoparticles displayed nanometer size, rod morphology, and negative surface charge with mesoporous structure belonging to the MCM-41 family (two-dimensional hexagonal). Regarding the results of BET adsorption and desorption isotherm analysis for Cis-Cur-MSNs and drug-free MSNs, pore diameter, pore volume, specific surface area, and drug-loaded pore area in MSNs were decreased. In the first 10 days, the prepared nanoparticles exhibited a relatively rapid release pattern for cisplatin and curcumin, and until the 35th day, the release of them from the MSNs continued slowly. CONCLUSION The cytotoxic effect of Cis-Cur-MSNs was significantly more than Cur-MSNs and Cis-MSNs in 24 and 48 h incubation time (p< 0.05). The results suggest that Cis-Cur-MSNs may be beneficial in the development of a cancer treatment protocol.