Objective To observe the safety and efficacy of liquid infiltration method to separate lenticule in small incision lenticule extraction (SMILE).Methods In this prospective study,72 patients were included.Randomly selected one eye was performed conventional method; the contralateral eye was performed liquid infiltration method.The corneal epithelium injury around the incision in surgery and the smoothness of the lenticule edge was observed under optical microscope.The differences of visual acuity,refraction,contrast sensitivity postoperatively between the two groups using independent samples t test.Results The corneal epithelium injuries were observed in 2 eyes in liquid infiltration method and 14 eyes in conventional method during surgery,the difference was statistically significant (x2=6.41,P＜0.01),the lenticule edges of liquid infiltration method were smoother than conventional method.The visual acuity,spherical equivalent (SE) and residual astigmatism of liquid infiltration method and conventional method 1 day postoperative were:4.98±0.06 and 4.89±0.53,+0.20±0.42 D and +0.30±0.37 D,0.14±0.40 D and 0.41±0.57 D respectively.The difference of residual astigmatism was statistically significant (t=-3.29,P＜0.05).The visual acuity,spherical equivalent and residual astigmatism of liquid infiltration method and conventional method 1 month postoperative were:4.99± 0.06 and 4.97±0.06,+0.11±0.40 D and +0.13±0.41 D,0.05±0.46 D and +0.36±0.66 D,respectively.The difference of residual astigmatism was statistically significant (t=-3.41,P＜0.05).The difference of contrast sensitivity was without statistically significant.Conclusion The liquid infiltration method makes the edge of lenticule smoother and effectively reduces the corneal epithelial injury and residual astigmatism.It is a safe and feasible skill in SMILE.