Objective To analyze the expression and clinical significance of 25-hydroxyvitamin D[25 (OH) D] and homocysteine (Hcy)in peripheral blood in elderly patients with schizophrenia (SCH).Methods A total of 140 elderly patients treated in the Veterans Administration Hospital from January 2021 to June 2023 were selected as the study objects,90 elderly SCH patients were included in the observation group,and 50 healthy elderly patients who underwent physical examination during the same period were included in the control group,the 25(OH)D and Hcy levels were compared between the two groups.The 90 elderly SCH patients were analyzed according to gender[male group(49 cases),female group(41 cases)],(age 60-70 years old group [45 cases],＞70 years old group [45 cases]),disease course (group A [＜6 months,27 cases],group B [6 months-5 years,40 cases],group C [＞5 years,23 cases]),positive and negative status scale (PANSS)score(group D [71-80 points,39 cases],group M [81-90 points,30 cases],group H [＞90 points,21 cases])were divided into different subgroups,and the 25 (OH)D and Hcy levels were compared in each subgroup.The correlation between 25(OH)D,Hcy and PANSS score were analyzed,and receiver operating characteristic(ROC)curve was also drawn to analyze the efficacy of 25(OH)D,Hcy and 25(OH)D combined with Hcy in the diagnosis of elderly SCH.Results The 25(OH)D of observation group was lower than that of control group,and the Hcy was higher than that of control group,the 25 (OH)D of the 70-year group was lower than that of the 60-70 year group,and the Hcy was higher than that of the 60-70 year group,the 25(OH)D of group C was lower than that of group B and group A,and the Hcy was higher than that of group B and group A.The 25 (OH)D of group H was lower than that of groups M and D,and the Hcy was higher than that of groups M and D,the differences were statistically significant (P＜0.05).Pearson correlation showed that 25 (OH)D was negatively correlated with PANSS score (r=0.520,P＜0.05);Hcy was positively correlated with PANSS score (r=0.479,P＜0.05).ROC results showed that the area under the curve (AUC),sensitivity and specificity of 25 (OH)D and Hcy combined in the diagnosis of SCH in the elderly were 0.925,98.90%and 92.00%,which were higher than the results of 25(OH)D and Hcy alone.Conclusion 25 (OH)D and Hcy are abnormally expressed in the serum of elderly SCH patients,and the combination of the two has significant effect in the diagnosis of elderly SCH patients,and has high clinical application value.