The influence of angle matching in rotor–stator interference (RSI) zone on natural circulation resistance (NCR) of circulating pump in natural circulation condition is illustrated by numerical method, and the analysis and optimization method of natural circulation based on loss coefficient curve are established through experiments. The mechanism and analysis formula of runaway speed are extracted, and the distribution diagram of Euler head density function (EHDF) is obtained to carry out image processing and analysis of secondary flow. Then, the optimal design interval of setting angle of impeller outlet under low flow resistance is acquired. As for the natural circulation loss of static parts, the optimal design interval of guide vane inlet angle and outlet angle with low flow resistance is obtained by analyzing the EHDF distribution diagram of the whole flow parts, which accounts for the position and reason of resistance. In this paper, the mechanism between runaway speed and loss coefficient curve is revealed and the resistance is optimized through the design and analysis of the RSI region, which provides theoretical methods for the analysis of the impeller performance of axial-flow circulating pump. Furthermore, it is a reference for the optimization design of natural circulation system.