New therapeutic approaches are still needed for effective malignant pleural mesothelioma treatment. The use of classical chemotherapy agents in combination with newly developed molecules may shed light on new therapeutic approaches. We aimed to determine the efficacy of panobinostat, alone and in combination with cisplatin, on cell survival and mRNA expression of FOXO3A, CCND1, and CASP9 genes in both mesothelioma and healthy mesothelial cell lines. Cells were treated with 1-100 μM cisplatin and 25-1000 nM panobinostat. Methylthiazol tetrazolium assays were performed to determine cell viability. mRNA expression levels of genes were analyzed with quantitative real-time polymerase chain reaction. Cisplatin and panobinostat exposure of the cells for 24 h resulted in decreased cell survival. The combined treatment was found to be more effective. No significant changes were observed with respect to CCND1 expression after exposure to agents alone or in combination. However, agents in combination resulted in upregulation of FOXO3A and CASP9 in MSTO-211H cells. Gene expression levels were not affected by any agents in healthy cells. Use of cisplatin in combination with new chemotherapeutic agents may reduce the toxic effects of cisplatin in normal cells and result in more effective removal of tumor cells.