The core loss of the grain-oriented silicon steel influences the energy loss of transformer. Pulse energy, point spacing, and scribing spacing are the three key parameters of laser scribing process, which determine the core loss of silicon steel. In this study, the relationship between the three key parameters and core loss reduction was investigated and analyzed. Experiments of laser scribing on 30Q130 silicon steel with different parameter combinations were implemented. The results showed that there was no obvious silicon coating burns in the surface of the steel after laser scribing and that the core loss reduction rate (reduction rate) significantly increased with the increasing laser energy density. However, when the energy density exceeded a certain range, the reduction rate decreased and gradually tended to a stable level. Hence, the parameters had significant influence on the reduction rate of core loss, and the two-factor interaction effects of reduction rate of core loss were prominent when parameters of high pulse energy, small point spacing, and small scribing spacing were selected. The optimization combination values of the three key parameters of laser scribing process on 30Q130 silicon steel was acquired by genetic algorithm–enhanced artificial neural network algorithm. For achieving high reduction of core loss, the optimized combination of pulse energy of 2.52 mJ, small point spacing of 0.22 mm, and small scribing spacing of 3.03 mm were selected, and the reduction rate of 13.12 % was verified through experiment.