Cisplatin-based chemotherapeutics represent a mainstay of lung cancer therapy, but resistance limits their curative potential. In the current study, we reported that Pidotimod, which is an immunostimulant and used for the prevention of acute respiratory infections, elevated cisplatin sensitivity, leading to the synergistic attenuation of tumor growth in mouse lewis lung cancer (LLC) model. With further exploration, we found that Pidotimod enhanced the anti-growth effect of cisplatin on LLC via promoting anti-tumor response, such as increased infiltration of dendrite cells (DCs) and CD8(+) T cells as well as enhancement of IFN-gamma and Granzyme B expression. In summary, Pidotimod affects the anti-tumor function of cisplatin via promoting anti-tumor immune response and these findings provide a novel approach for the development of therapeutic strategies for lung cancer. (C) 2020 Elsevier Inc. All rights reserved.