This paper presents a model for the solution of hydraulic transients with two-phase flow and fluid-structure interaction. Mathematical and numerical solutions are proposed and analyzed for the proper capture of the physical phenomena associated with the fluid compressibility and fluid celerity, which are variable in two-phase fluids, together with the disturbances generated by the fluid-structure interaction. The proposed solution for the model considers the simultaneous action of these phenomena. The developed numerical model is based on the solution of the mathematical model formed by a system of four partial differential equations, in which the necessary adaptations are integrated in fluid-structural equations and in the non-linear mathematical coefficients for the solution of the compressible and two-phase flow in question. Classical formulation is selected for the implementation of friction between fluid and pipe in the model. For the solution it is applied the method of characteristics and finite difference, with subsequent numerical integration. The validation of the results is carried out based on comparisons with experimental and analytical data.