Abstract As for the high-precision micro-hole formation in FR-4 copper clad laminate, the traditional mechanical drilling process is cumbersome and the degree of precision is low. The femtosecond laser is used to perform the single factor test and the orthogonal test on the copper clad laminate. The inlet diameter, outlet diameter and taper are used as the evaluation indexes to discuss the influence of the process parameters on the quality of micro-holes. The results show that the single pulse energy has the greatest impact on the quality of micro-holes and the repetition rate has the least influence. The optimal process parameter combination is set as single pulse energy of 29μJ, repetition rate of 92kHz, pulse number of 2112, and defocusing amount of 0.01mm. After these optimal process parameters are adopted, high-quality and high-precision drilling of FR-4 copper clad laminate can be performed to realize the rapid and efficient production of printed circuit boards.