In order to optimize the algorithm on contact pressure and interference magnitude of multi-layer interference cylinders, the effects of centrifugal force and temperature gradient on the performance of multi-layer interference cylinders are considered. The mathematical matrix model of contact pressure and interference magnitude of multi-layer interference cylinder is constructed under centrifugal force and temperature gradient. Four kinds of interference cylinder models are established, and the numerical solutions using finite element methods are compared with the analytical solutions. The results show that the contact pressure of each contact surface of multi-layer interference cylinder decreases with speed increase; the slip rate of contact pressure increases with speed increase; the maximum radial displacement of an interference cylinder under centrifugal force occurs at the outermost layer. The contact pressure of a multi-layer interference cylinder decreases linearly with the increase of temperature gradient. The analytical solution is basically consistent with the numerical solution, and the maximum relative error of midpoint is 11.62% and −7.69% under two factors. It means that the algorithm can provide a theoretical guide for the design of a multi-layer interference cylinder considering centrifugal force and temperature gradient.