Introduction: EGFR-sensitive mutations bilateral diffuse lung adenocarcinoma (LUAD) complicated with acute respiratory distress syndrome (ARDS) is relatively rare. It is important to consider whether EGFR-TKI can be simultaneously received when treating with extracorporeal membrane oxygenation (ECMO) and anti-infective therapy in these patients, and what adverse events should be noted? Case Presentation: We report a case of EGFR 19 exon-deficient bilateral diffuse LUAD complicated with ARDS. When treated with ECMO and anti-infective therapy, the patient received oral osimertinib anti-tumor therapy simultaneously. The tumor receded, but eventually irreversible thrombocytopenia developed. Conclusion: For patients with severe lung cancer, anti-tumor efficacy and adverse events should be closely observed during anti-tumor therapy.