Objectives To explore the effect of Paliperidone and Aripiprazole on the clinical efficacy， social function recovery， serum brain-derived neurotrophic factor（ BDNF） level and event-related brain potential N400 in first-episode acute schizophrenia. Methods This is a randomized， double-blind， controlled study. A total of 80 patients with first-episode acute schizophrenia who were treated in our hospital from August 2016 to August 2018 were selected and divided into observation group and control group according to random number table method， with 40 cases in each group. The patients in the control group were given Aripiprazole tablets with an initial dose of 10 mg per day， which was later increased by 5 mg per week according to their condition. The maximum dose was 30 mg per day. The patients in the observation group were given Paliperidone sustained-release tablets with an initial dose of 6 mg per day， which was increased by 3 mg per week according to their condition. The maximum dose was 12 mg per day. Both groups were treated continuously for 8 weeks. The clinical efficacy and adverse reactions in the two groups were observed. The recovery of social function， the level of BDNF and the change of event-related potential N400 were compared between the two groups. Results The total effective rate was 92.50% in the observation group， which was significantly higher than the 75% effective rate in the control group（ P＜0.05）. After the treatment， the positive and negative symptoms scale（ PANSS） scores of the two groups were both significantly lower than before the treatment， and the personal and social function scale（ PSP） scores of the two groups were both significantly higher than before the treatment （P ＜ 0.01）. After the treatment， the PANSS score of the observation group was significantly lower than the control group， and the PSP score was significantly higher than the control group（ P＜0.01）. After the treatment， the levels of BDNF in both groups were significantly higher than before the treatment（ P ＜ 0.05）， and the levels of BDNF in the observation group were significantly higher than the control group（ P＜0.05）. Under the matching conditions， the N400 latencies after the treatment were significantly shorter than before the treatment in both groups（ P＜0.01）， and the amplitude was higher than before the treatment（ P＜0.01）. Under the nonmatching conditions， the N400 latency of the observation group after treatment was significantly shorter than before the treatment（ P ＜ 0.05）. After the treatment， the Treatment Emergent Symptom Scale（ TESS） scores were（ 4.87±1.28） in the observation group， and（ 5.01±1.34） in the control group which showed no significant difference（ P ＞ 0.05）. There was no significant difference in the incidence of adverse reactions between the observation group（ 27.50%） and the control group（ 22.50%）（ P＞0.05）. Conclusions Paliperidone is effective in the treatment of schizophrenia. It can effectively improve the social and cognitive functions of patients， effectively regulate the level of BDNF and the change of event-related potential N400. It is well tolerated and worthy of clinical promotion.