Abstract: Cisplatin and its analogues are widely used in clinical chemotherapy of cancer. After intravenous injection and before reaching to DNA through the cell nucleus, cisplatin may interact with the serum and cellular proteins. Large amount of platinum binds to proteins in the blood and cytoplasm as well as nucleus via coordination bonds. These interactions are critical to the transportation, metabolism, accumulation, side effects and biological availability of the drug. Therefore, it is of great significance to study the binding behavior between platinum drugs and proteins. Mass spectrometry is a powerful technique for protein analysis, being very sensitive, high-throughput, less sample consumption and accurate, and has played an important role in the investigation of interactions between platinum based anticancer drugs and proteins. This article reviewed the coordination chemistry of platinum(Ⅱ) complexes, and demonstrated their possible mechanism of their anti-cancer effects in cells. In particular, this article focused on update advances on the mass spectrometric methodology for investigation of platinum-protein interaction, and summarized the interactions between amino acids/proteins and Pt-based drugs. The platinum(Ⅱ) based anticancer drugs, e.g. cisplatin, tends to bind to S-donors such as Met and Cys. Also His containing imidazole group can bind to Pt(Ⅱ) residues. Meanwhile, O-donors such as Tyr, Ser, Thr, Glu and Asp can interact with Pt(Ⅱ) as well. As the thiol and imidazole groups often occupy the important activity centers or metal binding sites of proteins, the interaction of platinum drugs with these amino acid side chains may directly lead to the loss of activity of these proteins, which may thus influence the cell viability in an extremely complicated way. These influences may enhance or decrease the activity of the drugs, or otherwise, lead to side effects and drug resistance. Nevertheless, these knowledge helps to expand our understanding of the metabolism and toxicity of platinum anticancer drugs, and contributes to the rational design of more low-toxic and efficient metal anticancer drugs.