Under slug flow conditions, electrical submersible pumps (ESPs) show a low efficiency due to Taylor bubbles, which cause pressure surging and gas pockets and the further deterioration of pressure boosting ability. In this study, a novel downhole bubble breaker is designed for mitigating the impact in ESP under slug flow conditions. The computational fluid dynamics-population balance model (CFD-PBM) coupled approach was used to calculate the bubble breaker's average bubble diameter to evaluate its efficiency. Meanwhile, experimental studies were conducted and compared with numerical results. Also, matlab and DIP-image technology was used to calculate the bubble diameter. Compared with experimental results, the simulation results agree well. Furthermore, the novel bubble breaker's performance was studied by orthogonal approach. The best result of range analysis is A2B3C4D1E4 (α = 30 deg, L = 300 mm, R = 2:1, vsg = 0.2 m/s, and vsl = 0.08 m/s), and sensitively analysis results present that the range of impact intensity are A (inlet angle) > E (superficial gas velocity) > B (total length) > D (superficial liquid velocity) > C (ratio of the gas–liquid channel). The optimal structure's bubble diameters are all less than that of the original structure, with a superficial gas velocity range of 0.2–0.6 m/s. The downstream bubble diameter of the optimal bubble is about 31.6% lower than the original structure at the maximum value point.