OBJECTIVE: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30, version 3.0) is a widely used disease-specific health-related quality of life (HRQoL) instrument, which has not been validated in Singapore. The purpose of this study was to investigate the validity and reliability of English and Chinese versions of the QLQ-C30 in Singaporean cancer patients who were receiving chemotherapy. METHODS: Cancer patients attending a chemotherapy center of a tertiary-referral hospital in Singapore were interviewed using an identical English or Chinese questionnaire containing the QLQ-C30, the Short Form 36 Health Survey (SF-36) and assessing socio-demographic status. Construct validity was assessed by relating QLQ-C30 scores to SF-36 scores, and reliability was assessed using Crobach's alpha. RESULTS: One hundred thirty subjects (English-speaking: 78) were interviewed. The subjects were mainly ethnic Chinese (Chinese: 96, Malay: 26, Indian: 4, others: 4), with a mean (SD) age of 49.3 (15.5) years. Generally, QLQ-C30 scale scores were strongly correlated with corresponding SF-36 scale scores for both English and Chinese versions. For example, Spearman's rank correlation coefficients between QLQ-C30 fatigue and SF-36 vitality scales were -0.72 and -0.69 for English and Chinese versions respectively (p <0.001 for both). Crobach's alpha was very close to or larger than 0.70 for all QLQ-C30 multi-item scales for both language versions except for the cognitive functioning scale for English version (alpha=0.43) and the pain scale for Chinese version (alpha=0.49). CONCLUSION: Both English and Chinese versions of the QLQ-C30 appear to be valid and reliable HRQoL instruments for use in Singaporean cancer patients.