Myeloid-derived suppressor cells (MDSCs) are heterogeneous and poorly mature cells of innate immunity that their population is increased substantially in cancer patients. MDSCs represent three subsets including CD14 monocytic (M), CD15 granulocytic (G) and Lin early precursor (e) cells. MDSCs release a number of factors that direct several tumorigenic-related events including immune evasion, angiogenesis and metastasis. Assessment of MDSCs can provide valuable information from cancer immunity state, and it can be an indicator of tumor prognosis. The cells can be targeted in combination with current immunotherapeutic schedules, and the outcomes were promising. The focus of this review is to provide an overview of MDSCs, their involvement in tumor-related immunosuppression, and their impact on cancer immunotherapy. Then, strategies are proposed to boost the power of immune system against MDSCs.