To investigate the effect of femtosecond laser helical processing parameters on the evolution of hole formation process, we use 304 stainless steel as the target material, select main parameters of the helical drilling by femtosecond pulsed laser, and design orthogonal experiments with 5 factors and 5 levels based on L25(56) orthogonal table. The significance levels of the ablation depth affected by 5 main parameters, such as the single pulse energy, repetition frequency, rotation rate, rate of focus down, and the air-blowing pressure, are analyzed. Based on the back propagation (BP) neural network, we establish the relationship model between the 5 main parameters and the ablation depth of the laser drilling. The data obtained from the orthogonal experiment are used to train the neural network. The generalization ability is tested by additional experiments. The results show that the prediction error of the relationship model is less than 3%. Moreover, the single factor experiment is designed to analyze the influence of the rate of focus down during the helical drilling. The effect of the different rates of focus down on the hole formation during the femtosecond laser helical drilling process is obtained.