Objective To investigate the expression of microRNA-199-3p(miR-199-3p)and miR-223-3p in the serum of patients with herpes zoster(HZ)and their predictive value for the development of postherpetic neuralgia(PHN).Methods A total of 512 HZ patients admitted to our hospital from February 2020 to November 2022 were included as the study group,and 512 individuals from the health examination cohort served as the control group.Serum levels of miR-199-3p and miR-223-3p were measured by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).HZ patients were followed up for 1 month and divided into PHN group and non-PHN group based on the presence of PHN.Logistic regression analysis was applied to analyze the factors associated with PHN in HZ patients.Receiver operating characteristic(ROC)curve was applied to assess the predictive value of serum miR-199-3p and miR-223-3p levels for the occurrence of PHN in HZ patients.Results The serum levels of miR-199-3p and miR-223-3p in the study group were lower than those in the control group(P<0.05).The incidence of PHN in HZ patients was 11.91%(61/512).In the PHN group,the proportion of patients with age≥50 years,combined with diabetes,hypertension,skin lesion type of gangrene,acute severe pain,skin lesion area>5%,time from onset to treatment>3 days,prodromal pain,elevated C-reactive protein,and elevated erythrocyte sedimentation rate were higher than those in the non-PHN group(P<0.05).Conversely,the proportion of patients with typical skin lesions and the serum levels of miR-199-3p and miR-223-3p were lower than those in the non-PHN group(P<0.05).Multivariate logistic regression analysis identified that age ≥ 50 years,skin lesion type,skin lesion area,time from onset to treatment,serum miR-199-3p and miR-223-3p as significant factors influencing the development of PHN in HZ patients(P<0.05).ROC analysis results revealed that the sensitivity of the combination of serum miR-199-3p and miR-223-3p had higher sensitivity in predicting PHN in HZ patients compared to single marker(P<0.05),and the area under the ROC curve(AUC)for the combined markers was significantly greater than for the individual markers(P<0.05).Conclusion The expression levels of miR-199-3p and miR-223-3p in the serum of HZ patients with PHN are both down-regulated,and both act as protective factors for HZ patients with PHN.They can be used as clinical biomarkers to predict HZ patients with PHN,and their combined use enhanced predictive accuracy.