BackgroundEwing’s sarcoma (ES) is the second most common malignant primary bone tumor in children and adolescents. Peroxiredoxin 2 (PRDX2) is an antioxidant enzyme.AimsHere, we investigated the role and mechanism of PRDX2 in the development of ES.Methods and resultsPRDX2 expression was knocked down in A673 and RDES cells by specific siRNA interference (si‐PRDX2). Knockdown of PRDX2 strongly inhibited the proliferation, growth, migration, invasion, and MMP9 activity and induces apoptosis of A673 and RDES cells. si‐PRDX2 significantly inhibited the phosphorylation of Akt and the expression of cyclin D1. The transcription factor that might regulate PRDX2 transcription was predicted with the JASPAR and UCSC databases, and analyzed using dual‐luciferase and Chromatin co‐immunoprecipitation experiments. SNAI1 could activate the transcription of PRDX2 by binding to predicted promoter binding site.ConclusionPRDX2 may be a potential therapeutic target for ES.