The synchronization and parameter estimation of an uncertain heterogeneous chaotic system with single-drive and multiple-response are investigated. By using Lorenz system to drive Yang system and Liu system simultaneously (parameters of the three systems are unknown), an uncertain heterogeneous chaotic system with single-drive and multiple-response is constructed. Based on Lyapunov stability theory and adaptive control method, the expression of adaptive controller and updating rule of parameters are given. Two different forms of mixed synchronization of the chaotic system with single-drive and multiple-response are investigated by introducing the scaling factor, and the unknown parameters are estimated. The feasibity of the method is proved theoretically. The simulation results show that the uncertain heterogeneous chaotic system with single-drive and multiple-response can achieve better synchronization and accurately estimate the values of all unknown parameters in the system.