Background: This study investigated the effect of oral nutritional supplements (ONS) on patients with esophageal cancer during radiotherapy. Materials and Methods: Patients with esophageal cancer undergoing radiotherapy were randomly divided into nutritional intervention (NI) and routine treatment (RT) groups. All patients received one-on-one nutritional counseling and dietary advice, and patients in the NI group received ONS. Body mass index (BMI), a patient-generated subjective global assessment (PG-SGA), serum albumin (ALB), hemoglobin (Hb), white blood cell (WBC) count, prealbumin (PA), and platelets (PLTs) were recorded before and after radiotherapy in both the NI group and the RT group. Further, the adverse reactions during the treatment were evaluated. Results: In the NI group, the BMI after radiotherapy was significantly higher than that before radiotherapy, and the PG-SGA score after radiotherapy was significantly lower than that before radiotherapy (p < 0.05). In the RT group, the levels of BMI, Hb, ALB, PA, PLTs, and WBC after radiotherapy were significantly lower than those before radiotherapy, and the PG-SGA score was worse after radiotherapy (p < 0.05). After radiotherapy, the levels of BMI, Hb, ALB, and PA in the NI group were similar to those in the RT group (p > 0.05); whereas the levels of WBC and PLTs in the NI group were lower than those in the RT group (p < 0.05). During the treatment, the toxic reactions of radiation esophagitis, myelosuppression, nausea, and vomiting were decreased in the NI group compared with the RT group. Conclusions: ONS can reduce weight loss and improve the nutritional status of patients with esophageal cancer during radiotherapy.

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