Aiming at the problem of interoperability between two information systems, a formalized method about interoperation research based on polychromatic sets theory is proposed, and the research steps of interoperability between two systems based on polychromatic sets theory are given. Firstly, the polychromatic sets theory is introduced and its contour is segmented to reflect the static and dynamic properties of the objects. The concept of single element polychromatic sets and its aggregation operation are given. Secondly, according to polychromatic set theory and its extensions, the research steps of interoperability between two information systems are given. The interoperability of the two systems are described in a single element polychromatic sets, and then the whole entity of interoperation is reflected through the union operation of two single element polychromatic sets. Finally, the validity of this formalized method is verified by the interoperability between hospital information system (HIS) and laboratory information system (LIS).