Objective To investigate the correlation between serum long chain non coding RNA-HOX transcript antisense interRNA(lncRNA HOTAIR)and microRNA-197-3p(miR-197-3p)levels with psychiatric symptoms and cognitive function in patients with schizophrenia(SCZ).Methods One hundred and eighteen patients with SCZ treated in the De-partment of Psychiatry of Guangzhou Medical University Affiliated Brain Hospital from April 2021 to March 2023 were se-lected as the study subjects(SCZ group),and 110 healthy individuals who underwent physical examinations during the same period were selected as the healthy control group.Real time fluorescence quantitative PCR(qRT PCR)was used to de-tect serum levels of lncRNA HOTAIR and miR-197-3p,and participants were evaluated for positive and negative symptom scale(PANSS)scores and cognitive function;Pearson Spearman correlation coefficient analysis of serum lncRNA HOTAIR and miR-197-3p levels,as well as their correlation with psychiatric symptoms and cognitive function;The evaluation value of receiver operating characteristic(ROC)curve analysis of serum lncRNA HOTAIR and miR-197-3p levels for SCZ.Results Compared with the healthy control group,the serum lncRNA HOTAIR expression level in the SCZ group increased,while the miR-197-3p level decreased(t/P=9.859/<0.001,19.191/<0.001).Bioinformatics predicts that there is a binding site be-tween lncRNA HOTAIR and miR-197-3p.The Pearson correlation analysis results showed a negative correlation between ln-cRNA HOTAIR expression and miR-197-3p expression in the serum of SCZ patients(r=-0.543,P<0.001).Compared with the healthy control group,the positive symptoms,negative symptoms,general pathological symptoms,and total score of the SCZ group were significantly increased(t/P=31.623/<0.001,28.219/<0.001,48.918/<0.001,39.574/<0.001).TMT,BACS,WMS-Ⅲ-SS,BVMT,HVLT,CPT,and SCWT were tested in a single test The color test score significantly decreased(t/P= 6.520/<0.001,7.666/<0.001,4.114/<0.001,8.191/<0.001,5.902/<0.001,4.985/<0.001,13.060/<0.001,8.938/<0.001).The lev-el of lncRNA HOTAIR in SCZ patients is positively correlated with negative symptoms and total score(r/P=0.498/<0.001,0.507/<0.001),and negatively correlated with TMT and CPT(r/P=-0.476/<0.001,-0.485/<0.001);MiR-197-3p is nega-tively correlated with negative symptoms and total score(r/P=-0.408/<0.001,-0.453/0.009),and positively correlated with TMT and CPT(r/P=0.449/0.001,0.517/<0.001).The AUCpredicted by serumlncRNA HOTAIR,miR-197-3p,and their com-bination for the occurrence of SCZ were 0.819,0.885,and 0.927,respectively.The combined prediction of AUC was signifi-cantly higher than their individual predictions(Z/P=4.580/<0.001,2.953/0.003).Conclusion SerumlncRNA HOTAIRis up-regulated and miR-197-3p is downregulated in SCZ patients,which is associated with psychiatric symptoms and cognitive function.