To understand complex immunological mechanisms alongside avoiding huge experimentation costs, mathematical modelling has been used in the development of anticancer drugs. In this paper, a mathematical model is proposed to describe the roles of hypoxia-inducible factors (HIFs) (transcription factors released by tumors in response to a decrease in available oxygen), in the interactions between the tumor and the immune system. For this purpose, a previously published model of immunotherapy with dendritic cells (DCs) is extended so as to incorporate the treatment with an HIF inhibitor drug. Based on the experimental data, this extended model is calibrated for the model parameters leading to an acceptable level of the mean absolute percentage error in the validation phase. The proposed model is capable of determining the most effective immunosuppressive mechanism by which the HIF effects, and the effect of HIF on DCs and inflammatory factors of the immune system has been found to be of great importance.