In this paper, we propose the Phy-DRL: a physics-model-regulated deep reinforcement learning framework for safety-critical autonomous systems. The Phy-DRL is unique in three innovations: i) proactive unknown-unknowns training, ii) conjunctive residual control (i.e., integration of data-driven control and physics-model-based control) and safety- \& stability-sensitive reward, and iii) physics-model-based neural network editing, including link editing and activation editing. Thanks to the concurrent designs, the Phy-DRL is able to 1) tolerate unknown-unknowns disturbances, 2) guarantee mathematically provable safety and stability, and 3) strictly comply with physical knowledge pertaining to Bellman equation and reward. The effectiveness of the Phy-DRL is finally validated by an inverted pendulum and a quadruped robot. The experimental results demonstrate that compared with purely data-driven DRL, Phy-DRL features remarkably fewer learning parameters, accelerated training and enlarged reward, while offering enhanced model robustness and safety assurance.