The Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q) is not currently available in Chinese. Besides, penicillin allergy (PA) is a worldwide public health challenge, and delabeling inauthentic PA can improve clinical and economic outcomes. However, its effect on health-related quality of life (HRQoL) remains poorly known. Objective: The study objective is to translate and validate a Chinese version of DrHy-Q and investigate the effect of PA delabeling on HRQoL using DrHy-Q. Methods: A Chinese DrHy-Q was translated then completed by patients with drug allergy labels for psychometric validation. Afterwards, another cohort of patients finished the Chinese DrHy-Q before and after their PA workup for pre-post comparison. Results: A total of 130 patients were studied. Sixty-three patients (79.4% female; median age = 59 ± 15 years) completed the Chinese DrHy-Q for validation (mean score = 38.9 ± 23.5). It demonstrated excellent internal consistency (Cronbach α = 0.956; 95% confidence interval [CI], 0.939-0.971) and test-retest reliability (intraclass correlation coefficient = 0.993 [95% CI, 0.969-0.998]). Construct validity was confirmed by its one-dimensional structure in factor analysis. Divergent validity was established because only 2 (out of 9) SF-36 scales showed weak negative correlations to DrHy-Q. Patients with multiple implicated drugs presented significantly higher DrHy-Q scores than those with only a single drug (42.0 ± 22.5 vs 28.7 ± 24.4; P = 0.038), showing discriminant validity. Subsequently, another 67 patients (73.1% female; median age = 56 ± 15 years) underwent PA investigations and completed their pre-post DrHy-Q. A significant drop in DrHy-Q score was shown (40.8 ± 21.7 vs 26.6 ± 22.5; Cohen's d = 0.964; P < 0.001), reflecting improvement in HRQoL. Conclusion: The Chinese DrHy-Q is reliable and valid for HRQoL assessment. PA delabeling significantly benefits patients' HRQoL. Future larger-scale studies are warranted to corroborate our findings.