Mediator 19 (Med19) is a component of the mediator complex which is a coactivator for DNA-bindingfactors that activate transcription via RNA polymerase II. Accumulating evidence has shown that Med19 playsimportant roles in cancer cell proliferation and tumorigenesis. The involvement of Med19 in sensitivity to thechemotherapeutic agent cisplatin was here investigated. We employed RNA interference to reduce Med19expression in human non-small cell lung cancer (NSCLC) cell lines and analyzed their phenotypic changes. Theresults showed that after Med19 siRNA transfection, expression of Med19 mRNA and protein was dramaticallyreduced (p<0.05). Meanwhile, impaired growth potential, arrested cell cycle at G0/G1 phase and enhancedsensitivity to cisplatin were exhibited. Apoptosis and caspase-3 activity were increased when cells were exposedto Med19 siRNA and/or cisplatin. The present findings suggest that Med19 facilitates tumorigenic properties ofNSCLC cells and knockdown of Med19 may be a rational therapeutic tool for lung cancer cisplatin sensitization.