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Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by severe itching accompanied by multiple nodules throughout the body. There is currently no effective drug-targeted treatment for PN. Dupilumab is a fully human monoclonal antibody which can suppress the Th2 inflammatory reaction. We aimed to assess the efficacy and safety of dupilumab in PN. There were 29 PN patients who received dupilumab treatment for four months. Serum total immunoglobulin E (Ig E), eosinophil counts, dermatology life quality index (DLQI), and numeric rating scale (NRS) were assessed on patients before and after treatment. We count the vaccination of novel coronavirus pneumonia (COVID-19) in patients and the impact on PN and treatment measures after vaccination. Plotting was performed using GraphPad Prism8, and the statistical analysis was performed using PASW Statistics18. The eosinophil counts in patients higher decreased to normal, and the Ig E levels gradually decreased and tended to normal levels after receiving dupilumab injection. The average DLQI score at the baseline was 23.93 ± 0.66 and decreased to 11.66 ± 0.55 ( P < 0.01 ) and 1.83 ± 0.22 ( P < 0.01 ) at 1-month and 6-monthfollow-up of treatment, respectively. The average NRS score at the baseline was 9.79 ± 0.08 and decreased to 3.52 ± 0.23 ( P   <   0.01 ) and 0.31 ± 0.15 ( P   <   0.01 ) at the 1-month and 6-monthfollow-up of treatment, respectively. Our study shows that dupilumab has achieved good efficacy in PN with few adverse reactions and high safety. We can recommend that patients follow the advice of specialists to be vaccinated and under the condition of stable disease, separated from dupilumab treatment for one week.