Adaptation to hypoxic enviroment is crucial for tumor survival and metastatic spread. Hypoxia induced factor - 1α (HIF-1α) is a key factor in this adaptation by stimulating the production of proangiogenic factors and by inducing enzymes needed for anaerobic metabolism. Histone deacetylase inhibitors (HDACI), including resveratrol inhibit HIF-1α expression and can contribute to inhibiton of tumor growth through potent antiangiogenic effect. The purpuse of this research was to explore chemosensitive potential of resveratrol and its nanocrystal formulation (NK Res) in combination with cisplatin on tumor angiogenesis inhibition, tumor growth and macrophage polarisation in mice bearing solid form of Erlich ascites tumor (EAT) exposed to systemic hyperthermia. After subcutaneous (sc) injection of 1 × 106 EAT cells in thigh of Balb/c mice, mice were treated with resveratrol and/or NK Res per os during five consecutive days starting from the second day after tumor injection and cisplatin intraperitoneally (ip) at a dose of 2.5 mg/kg on the day 10 and 12 and at a dose of 5 mg/kg on the day 15. Right after, mice were exposed to systemic hyperthermia lasting for 15 min at a temperature of 41 °C. Level of histone deacetylases (HDAC), HIF-1α, heat shock protein-70 and -90 (HSP-70/90), vascular endothelial growth factor (VEGF) and vascular density, metalloproteinases-2 and 9 (MMP-2/9), inducible synthase of nitric oxide (iNOS) and arginase were determined in the tumor tissue with monitoring of tumor growth and volume and animal survival. Summarizing the obtained data, resveratrol can enhance the antitumor effect of cisplatin by modulating HDAC activity and the level of HSP70/90, thus contributing to direct toxicity on tumor cells, overcoming resistance and tumor growth, and consequently increasing the survival of mice. Hyperthermia enhances local blood flow in tumor and increases cisplatin accumulation of cisplatin within tumor tissue and remodulates tumor microenviroment through M1 macrophage activation and immune system on tumor cells. NK Res has better bioavailability, solubility and retention in specific tumor vasculature and thereby increases antitumor and antiangiogenic effect of cisplatin in physiological conditions, while in hyperthermic conditions it can slightly lower the effect of cisplatin through tumor microenviroment changes and HIF-NO signalisation.