In this paper, a closed-form frequency equation of the pipe-in-pipe (PIP) structure with arbitrary boundaries is obtained. The frequency equation is derived from Green’s function of the transverse forced vibration of the PIP structure and takes into account the effects of internal two-phase flow and axial pressure. The reliability of the method in this paper is proved by comparison with the published literature. In the numerical discussion part, the PIP structures with clamped-clamped, clamped-free, and elastic boundary conditions are used as examples to discuss. The effects of equivalent stiffness coefficient, internal flow velocity, and gas volume fraction on the stability of PIP structure are studied. The results show that the stability of the PIP structure is better than that of the single-pipe structure, and the greater the equivalent stiffness coefficient of the elastic layer, the higher the critical flow velocity of the structure. In addition, a modal conversion phenomenon existing in the PIP structure is discovered. There are different forms of modal conversion for different boundary conditions, and the modal conversion makes the order of instability of the PIP structure different from that of a single-pipe. The conclusion of this paper has positive significance for the dynamic research of PIP structure.