A Simplified Chinese version of the EORTC QLQ-BR53 was evaluated using responses from 233 patients with breast cancer in China by assessing the construct and criterion-related validity, internal consistency and test-retest reliability, and responsiveness as measured by score changes of the scales. Internal consistency reliability measured by Cronbach's coefficient alpha is greater than 0.75 for most multi-item scales except cognitive functioning (0.41) and breast symptoms (0.71). Test-retest reliability coefficients for all domains are greater than 0.80 with the exception of physical functioning (0.65), social functioning (0.75), appetite loss (0.75), diarrhea (0.72), and body image (0.72). Correlation and factor analysis among domains and items showed good construct validity for both QLQ-C30 and QLQ-BR23. Score changes over time were observed in most domains except emotional functioning, global health status/QOL, dyspnoea, constipation, diarrhea, financial difficulties, sexual functioning, sexual enjoyment, and breast symptoms. Therefore, the Simplified Chinese version of QLQ-BR53 shows reasonable validity, reliability, and responsiveness and can be used to measure QOL for Chinese patients with breast cancer.