Hyponatremia is the most common electrolyte abnormality in hospitalized patients. The objective of this study was to identify risk factors for hyponatremia during chemotherapy in children. A total of 111 consecutive pediatric patients (age, 0 to 18 y) with hematological malignancy (n=87) or solid tumor (n=24) who received chemotherapy in our hospital between 2010 and 2014 were enrolled. The number of chemotherapy cycles reviewed was 472, with a median of 3 (range, 1 to 8) per patient. Hyponatremia was defined as a serum sodium level of <135 mmol/L. Hyponatremia was observed in 80 of 111 (72%) patients, and 138 of 472 (29%) cycles. Neurological sequelae were seen in 2 of 111 (2%) patients, and 2 of 472 (0.4%) cycles. Multivariate logistic regression identified age 10 to 18 years (odds ratio [OR]=3.24, 95% confidence interval [CI], 2.07-5.07), total parenteral nutrition (OR=8.15, 95% CI, 2.17-30.5), first or second chemotherapy cycle (OR=1.74, 95% CI, 1.12-2.70) as independent risk factors for hyponatremia. Clinical conditions of patients and chemotherapeutic agents may have a profound impact on the development of hyponatremia. Patients with these factors should be managed carefully to prevent severe symptoms and sequelae caused by hyponatremia.