CASE PRESENTATION: A 64-year-old non-atopic man with lung cancer was admitted in our unit for chemotherapy. He had two similar allergic episodes with good outcomes after active treatment in the past month. For the first time, allergic reaction, including urticaria, dyspnea, appeared within a few minutes after the intravenous administration of 800mg pemetrexed disodium for injection followed by 40mg omeprazole. In the second preparation we adjusted the medication order. Omeprazole (40mg) was infused firstly, unfortunately, severe allergic event occurred within 10 minutes. The patient experienced urticaria, wheeze, decline of oxygen saturation (less than 90%), low systolic blood pressure (less than 90 mmHg), and tachycardia (more than 130 beats per min). Serum IgE measurement was significantly higher than that in normal subjects within 24 h after the second event and intradermal skin test with omepazole was positive (the patients had signed written informed consent before treatment and check). He received immediate treatment with oxygen inhalation followed by intravenous dexamethasone and promethazine, and the symptoms disappeared in less than 2 hours. Under strict medical supervision, no adverse reaction was found induced by lansoprazole for replacement therapy after skin test came back negative.