Objective To analyze the efficacy and safety of domestic paliperidone sustained-release tablets in the treatment of stable schizophrenia．Methods A total of 108 patients with stable schizophrenia admitted to Zhumadian Second People's Hospital from October 2021 to October 2023 were divided into control group（taking the original paliperidone sustained-release tablet）and observation group（taking domestic paliperidone sustained-release tablet）by random number table method,with 54 cases in each group．The change of Positive and Negative Symptom Scale（PANSS）was used as the efficacy measure,and the change of incidence of adverse reactions and Treatment Emergent Symptom Scale（TESS） score was used as the safety measure．Results After treatment,PANSS scores in both groups were lower than before treatment,and the differences in scores at different time points in the groups were statistically significant（t=22.147,4.513,3.431,21.369,3.927,3.601,the P values were<0.001,<0.001,0.001,<0.001,<0.001,<0.001,respectively）．However,there was no significant difference in scores at different time points between the groups（t=0.281,0.043,0.150,P=0.779,0.966,0.881）．There was no significant difference in the incidence of adverse reactions between observation group（14.81%）and control group（12.96%）（χ²=0.090,P=0.765）．TESS scores were similar between the two groups,and adverse reactions were mild（t=0.185,P=0.856）．Conclusions The domestic paliperidone sustained-release tablets can improve the symptoms of stable schizophrenia patients,and the side effects are slight,and the efficacy and safety are comparable to the original agent．