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This study aimed to assess generic health-related quality of life (HRQoL), pain intensity, and anxiety levels and the relationship between the three aspects in healthy young Chinese orthodontic patients in the early stage of orthodontic treatment. We enrolled 252 eligible participants (10–29 years old) to complete validated Chinese versions of questionnaires, including the State-Trait Anxiety Inventory (S-AI), the visual analogue scale (VAS), and the Short-Form 36-Item Health Survey (SF-36) at baseline and on days 1, 2, 3, 7, 14, and 30 after initial archwire placement (SF-36 only at baseline and day 30). The response rate was 96% (243 of 252). SF-36 had moderate reliability (Cronbach's alpha coefficient exceeding 0.7, good fit on day 30). Statistical significant changes were observed in physical function (P<0.01), body pain (P=0.01), and general health (P<0.01) domains. Spearman correlation coefficients for SF-36 with S-AI were −0.131~−0.515 (P<0.05); SF-36 with VAS were −0.141~−0.273 (P<0.05), indicating significant but moderate negative correlations between HRQoL and pain/anxiety. Overall, the application of SF-36 in assessing HRQoL is reluctantly suitable for young Chinese orthodontic patients in the early stage of orthodontic treatment. Early treatment-related pain and anxiety are important factors in HRQoL. [ABSTRACT FROM AUTHOR]