Background <p>Oncologic patients are vulnerable to prolonged or severe COVID-19 due to immunosuppression and comorbidities. Our initial Phase I/II clinical trial has showed​ that epigallocatechin-3-gallate (EGCG), a catechin monomer isolated from tea, exhibits favorable safety profiles with therapeutic effects against COVID-19 pneumonia. This phase II, open-label, randomized controlled trial further evaluated the efficacy and safety of 7-day aerosolized epigallocatechin-3-gallate (EGCG) in oncologic patients with COVID-19 pneumonia.</p> Methods <p>This trial was conducted from June 2023 to May 2024. Patients were randomized (2:1) to receive aerosolized EGCG plus standard treatment or standard treatment alone. The primary endpoint was CT imaging improvement. Secondary endpoints included symptom resolution and the safety of EGCG.</p> Results <p>114 patients were randomized, with 108 eligible (71 in EGCG group, 37 in control group). The EGCG group showed significantly greater CT improvement (<i>P</i> = 0.004) and faster symptom resolution for fever <i>(P</i> = 0.035), cough (<i>P</i> = 0.048), and dyspnea (<i>P</i> = 0.015). Improvement rates were higher in the EGCG group for fever (95% confidence interval: 1.380 -10.352) and dyspnea (95% confidence interval:1.750-60.446). Post-treatment lactate dehydrogenase levels were significantly lower in the EGCG group (<i>P</i> = 0.028). Safety profiles were comparable, with only mild adverse events observed in the EGCG group.</p> Conclusions <p>Aerosolized EGCG significantly improved both radiological and clinical outcomes with a favorable safety profile in oncologic patients with COVID-19 pneumonia, although broader application requires further validation in larger multi-center trials.</p> Trial registry <p>ClinicalTrials.gov, TRN: NCT06924749, Registration date: 22 August 2023.</p>