Objective To explore the influence of root canal preparation with mechanical and manual nickel-titanium instruments on the operation time and treatment effect during root canal therapy of pulp disease of deciduous teeth in children. Methods 103 children with pulp disease of deciduous teeth in the hospital from January 2020 to March 2021 were selected for the study.According to the random number table method, the children were divided into manual group and mechanical group. The manual group (n=51) was treated with manual nickel-titanium enlarged file for root canal preparation, and the mechanical group (n=52) underwent root canal preparation with mechanical nickel-titanium instrument. The root canal preparation effect and filling effect, postoperative complications, root canal cleanliness, postoperative pain grading and masticatory function were compared between the two groups. Results The root canal preparation time in mechanical group was significantly shorter than that in manual group (P<0.05), and the root canal preparation effect and root canal filling effect were significantly better than those in manual group (P<0.05). The incidence rate of postoperative complications was 5.77% in mechanical group and that in manual group was 19.61% (P<0.05). The root canal debris score, anvil fouling score and postoperative pain in mechanical group were significantly lower or milder than those in manual group (P<0.05). At 1 year of follow-up after treatment, the occlusal force and masticatory efficiency were significantly higher in mechanical group than those in manual group (P<0.05).Conclusion Compared with manual nickel-titanium enlarged file, mechanical nickel-titanium instrument has a shorter root canal treatment time, and the latter one is more conducive to improving the root canal preparation effect and filling effect. Mechanical nickel-titanium instrument has high root canal cleanliness and can relieve the postoperative pain of affected teeth, with good long-term efficacy