Objective: To analyze the effect of two approaches of microsurgery in the treatment of pituitary tumor. Methods: The main body of this study was 69 patients with pituitary tumor who came to the hospital between December 2016 and December 2019. Taking the coin method as the standard, group A underwent nasal-sphenoid sinus approach with 36 cases; group B underwent transcranial approach with 33 cases. The treatment effects were compared. Results: The total effective rate of group A was 94.44%, and that of group B was 72.73%; the therapeutic index of group A was better than that of group B; the complication rate of group A was 8.33%, and that of group B was 30.30% (P<0.05). After treatment, the tumor volume of both groups decreased, and group A was smaller than group B (P<0.05). Conclusion: Nasal-sphenoid sinus approach for patients with pituitary tumors can improve the treatment index, enhance the curative effect, reduce the size of the tumor, and have better safety.