Objective To investigate the changes of serum micrornA⁃21（miR⁃21）and hypoxia⁃induced⁃ factor⁃1α（HIF⁃1α）levels before and after treatment in patients with herpes zoster and their evaluation value for postharcoma neuralgia. Methods From June 2019 to April 2022，183 patients with herpes zoster in our hospital were selected，of which 122 were chosen as training group to establish the model，and another 61 as validation group to verify the model. At the same time，61 healthy subjects were selected as control group. All patients with herpes zoster were treated with conventional regimens. Serum miR⁃21 and HIF⁃1α levels were detected in all the three groups. Related factors of posthumous neuralgia in the training group and the value of serum miR⁃21 and HIF⁃ 1α levels in the evaluation of postharcoma neuralgia was analyzed. Results The levels of serum miR⁃21 and HIF⁃ 1α in the training group before treatment and one week after treatment were higher than those in the control group （P < 0.05），and the levels of serum miR⁃21 and HIF⁃1α in the training group after one week of treatment was lower than those in the same group before treatment（P < 0.05）. Serum miR⁃21 and HIF⁃1α levels were still independent influencing factors for postherpetic neuralgia in patients with herpes zoster（P < 0.05）. The AUC of the logistic regression model in the training group was 0.876. In the validation group，that was 0.869. Conclusion Serum miR⁃ 21 and HIF⁃1α express highly in patients with herpes zoster，and their levels significantly decrease after treatment. Elevated levels of miR⁃21 and HIF⁃1α are independent risk factors for postherpetic neuralgia in patients. The risk model constructed based on serum miR⁃21 and HIF⁃1α level has high evaluation efficiency.