Objective To study the efficacy of lurasidone and risperidone in patients with acute schizophrenia (SCH). Methods 92 cases of acute SCH patients admitted to our hospital from January 2022 to December 2023 were selected as the study objects. Patients were divided into lurasidone group and risperidone group with 46 cases in each group by random number table method. Lurasidone group was treated with lurasidone, risperidone group was treated with risperidone. The therapeutic effect, cognitive function indicators [brain-derived neurotrophic factor (BDNF), glial cytogenic neurotrophic factor (GDNF), homocysteine (Hcy)] levels, clinical symptom severity [Positive and Negative Syndrome Scale (PANSS)] and incidence of adverse reactions were analyzed and compared between the two groups. Results The total effective rate of lurasidone group was 91.30%, which was significantly higher than that of risperidone group (71.74%) (P < 0.05). After treatment, the levels of BDNF and GDNF in both groups were significantly higher than before treatment, and the levels of Hcy were significantly lower than before treatment, and the changes of BDNF, GDNF and Hcy in Lurasidone group were significantly greater than those in risperidone group (P < 0.05). After treatment, the positive symptom score and negative symptom score of both groups were significantly lower than before treatment, and the positive symptom score and negative symptom score of lurasidone group were significantly lower than those of risperidone group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion Compared with risperidone, lurasidone has a better effect in acute SCH patients, which can improve the therapeutic effect, relieve the clinical symptoms and improve the cognitive function of patients, and has a good therapeutic safety.