The objective of this study was to investigate the expression of serum miR-7 and erythrocyte sedimentation rate (ESR) levels in patients with acute herpes zoster (HZ) and their evaluation value for postherpetic neuralgia (PHN). A total of 98 patients with acute HZ and 97 healthy people were enrolled in this study. The levels of miR-7 and ESR were analyzed in patients with HZ and healthy people. According to whether PHN occurred within 3 months after lesion regression, the patients were divided into HZ patients with PHN and HZ patients without PHN, and the levels of miR-7 and ESR of the two groups were analyzed. The clinical indicators of the PHN and non-PHN groups were analyzed by univariate and multivariate analysis, and the risk factors affecting PHN were evaluated. ROC curves were established to evaluate the diagnostic value of miR-7 and ESR in PHN. Compared with the healthy control group, miR-7 and ESR levels of patients with HZ showed a significant downward and upward trend, respectively. Compared with the patients without PHN, patients with PHN had decreased miR-7 and increased ESR. MiR-7 and ESR were significantly correlated with clinical indicators such as VAS scores in patients with HZ. Multivariate logistic regression analysis showed that miR-7 and ESR were independent factors influencing the occurrence of PHN. ROC analysis revealed that the combination of miR-7 and ESR had high clinical diagnostic accuracy for PHN. The reduction of miR-7 and the increase of ESR are independent risk factors for PHN in HZ patients, and the ROC curve constructed based on the clinical expression levels of miR-7 and ESR showed high clinical diagnostic value for PHN.