Chemical proteomics, as an important branch of proteomics, integrates methods from synthetic chemistry, cell biology, and mass spectrometry. It aims to design small molecule (SM) probes to elucidate the mode of action of SMs and the function of protein in drug discovery. Within the context of natural products, chemical proteomics can be used to identify the protein binding partners or targets of SMs in living cells. Chemical proteomics consists of two key steps: