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Background Adult acute leukemia (AL) patients who receive chemotherapy usually experience multiple symptoms during the treatment course. The symptom clusters (SCs) as well as subsets of concurrent symptoms in AL patients have not yet been demonstrated. Objective To investigate the SCs of adult AL patients who were receiving chemotherapy and to determine their correlations with functional performance. Methods A total of 132 hospitalized adult AL patients were included in this study. A cross-sectional survey aimed to examine symptoms and functional performance was conducted. The patients' symptoms were assessed using the Chinese version of the Condensed Memorial Symptom Assessment Scale, and functional performance was evaluated through activities of daily living and quality of life. Results We identified 4 SCs in adult AL patients: psychological SC, pain-fatigue-sleep SC, dry mouth-constipation SC, and nutrition-impaired SC. The psychological SC was the most common and most distressing SC. The different SCs were each differentially correlated with patient characteristics. The distress of the psychological SC, pain-fatigue-sleep SC, and nutrition-impaired SC was adversely correlated with functional performance. Conclusions Adult AL patients undergoing chemotherapy experience multiple symptoms that can be further categorized into 4 SCs. The distress from some SCs is negatively associated with patients' functional performance. Implications for practice Symptom burden remains a major problem for adult AL patients undergoing chemotherapy. Identifying SCs of AL patients should be the basis for accurate and cost-effective interventions. Personalized SC management may improve the functional performance and healthcare quality of adult AL patients.