Abstract: Cancer immunotherapy based on immune checkpoint inhibitors (ICIs) represents the promising advances over the past decade. Demonstrating unprecedented extension of patient survival, antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1) quickly became the promising novel treatment in anti-cancer therapeutics nowadays. So, immunotherapy of cancer has entered into a new phase. Clinical trials and practices conducted simultaneously by oncologists both in China and the developed countries furtherly proved the clinical efficiency of agents targeting ICIs in treatment of a wide array of cancer types. However, despite the success of ICIs, side effects of antibody targeting ICIs gradually emerged during the widespread use in clinic, including the low overall response rates (ORRs), acquired resistance to these agents, and various immune-related adverse events (irAEs), of which are worthy of attention of the oncologists. This paper summarized the recent progress of ICIs in clinics, discussed the above challenges, and proposed the strategy for increasing benefits of the ICIs therapy.