This paper presents and verifies a novel Cartesian impedance control of the flexible joint manipulator for physical human–robot interaction application based on virtual decomposition control approach. Firstly, the Cartesian impedance control based on virtual decomposition control (VDC) is presented, and the asymptotical stability of the controller is proven by Lyapunov stability theorem. Compared with traditional methods based on singular perturbation, this method can greatly reduce the computational loads and is more suitable for real-time application. Then, a Cartesian force-feedback path planning combined with Cartesian impedance control based on VDC was used to keep the real contact force within the desired value to protect the manipulator and objects as a force, position, velocity and acceleration sensor, and the sensor can be configured freely by regulating the stiffness, damping and inertia, so the manipulator can interact with human (or unknown environment) in a friendly manner. The experimental results illustrate the validity of the developed VDC-based impedance control approach.