Abstract: Objective： To compare the influences of Er: YAG laser irradiation with different working parameters on dentinal tubule occlusion, and to find the best combination of parameter settings. Methods：54 dentin discs and dentin hypersensitivity models formed by 0.5 mol/L EDTA demineralization were prepared and randomly divided into 9 groups each containing 6 specimens according to different output power, irradiation time and irradiation distances of the Er:YAG laser. A table for orthogonal optimization experiment was designed. Specimens were evaluated with regard to dentin orifice occlusion under scanning transmission electron microscopes (SEM). Results： SEM showed most of the dentinal tubules in the demineralization group were clearly open, while they were partially or fully occluded by Er:YAG irradiation. There were significant differences between groups (P<0.05). Conclusions：Subject to working parameters, Er:YAG laser irradiation can be effective in narrowing or occluding the dentinal tubules. The best combination of working parameters with the most influential irradiation distance is: Distance = 2.0 cm, Power = 0.2 W and Time = 30 s.