Positive ion mode of electrospray ionization mass spectrometry (ESI-MS) has been used for the detection and study of protein interaction. From the measurement of molecular mass of the intact complex and individual binding partners, the binding stoichiometry can be derived. In our work, one basic protein, hen egg white lysozyme (HEWL) as an anion receptor shows high sensitivity and selectivity responses to most oxoanions detected by ESI-MS. But neutral protein, such as insulin, does not response to anions. It was found that HSO4-, IO4-, ClO4- (,) H2PO4-, HCO3-, and AcO- have strong affinity to interact with HEWL under present condition, but HSO3-, NO3-, Cl- and F- could not be trapped by HEWL. ESI-MS condition and concentration of anions are considered. This is an important evidence obtained by mass spectrometry for the distribution of anion recognition with a native protein.