Background: Acute leukemia (AL) not only impairs the quality of life (QOL) of patients, but also affects that of their family caregivers (FCs). Studies on QOL of AL patients and their FCs are limited. This study aimed to evaluate the QOL of AL patients and their FCs, and to explore the factors associated with QOL of patients and of FCs. Methods: A multicenter cross-sectional study was conducted. The QOL of 196 patient-FC dyads was assessed. The Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) was used for patients, and the 36-item Short-Form Health Survey (SF-36) was used for FCs. Independent-samples t-tests or one-way analysis of variance were used to compare QOL subscale scores between groups with different sociodemographic/clinical characteristics. Multiple regression analysis was conducted to identify the factors associated with QOL of AL patients and their FCs. Results: The total FACT-Leu score for AL patients was 76.80 ± 16.44, and the physical component summary (PCS) and mental component summary (MCS) scores for FCs were 64.67 ± 15.44 and 52.50 ± 13.49, respectively. All QOL subscales for patients (t = 12.96-34.73, p < 0.001) and FCs (t = 2.55-14.36, p < 0.05), except role emotional (t = - 0.01, p = 0.993), were lower than those reported in previous studies. Sex, employment, and chemotherapy were significantly associated with total FACT-Leu score in AL patients (p < 0.05). Age, sex, marital status, education, employment, and relationship to patients were significantly associated with SF-36 PCS or MCS (p < 0.05). Conclusions: AL patients and their FCs both have lower QOL than the population in previous studies. These findings suggest that not only AL patients' physical and mental health but also overall family QOL should be assessed. Interventions supporting patient-FC dyads should be developed to improve their QOL.