Abstract: In order to investigate the influence of multi-factor coupling on thermal error of high-speed motorized spindle, a new orthogonal experimental design method based on wireless communication technology was proposed. A temperature acquisition label composed of temperature sensor PT100, microprocessor STM8S and wireless transceiver module nRF905 is designed, which can realize intelligent wireless monitoring of temperature signals at distributed measuring points, satisfying the convenience of multi-factor thermal error experiment and data acquisition. The experimental scheme is designed based on the orthogonal experiment method, which not only reduces the number of experiments, but also solves the problem of uneven number of multi-factors. Direct analysis, range analysis and variance analysis of the data show that cooling factors have the greatest influence on thermal error, followed by running time. The optimal scheme for spindle running is cooling water temperature: 18 ℃~20 ℃, cooling water flow: 2.5 L/min, rotating speed: 20 000 r/min, running time: 30 min.