The H2+He fluid mixture will be dissociated into a three-component mixture composed of H2 molecules, H and He atoms at high temperatures and high pressures. The dissociation energy of H2 molecule will be lowered due to the interactions between all these particles. In this paper, the self-consistent fluid variational theory is used to calculate the equation of state of H2+He fluid mixture in the region of partial dissociation, in which the various interactions between particles and the correlation contributions to the dissociation energy caused by both the temperature and pressure effects are taken into account. The dissociation degree and thermodynamic parameters are obtained from nonideal dissociation equilibrium, which is determined self-consistently by the free energy function. Comparison was made with the available shock-wave experiments, other theoretical calculations and Monte Carlo simulations.