In recent years, Epidermal Growth Factor receptor-tyrosine Kinase Inhibitor (EGFR-TKI) has become the standard first-line treatment for patients with positive driver gene mutations. The role of whole brain radiation therapy (WBRT) in non-small cell lung cancer with multiple brain metastases has also been reassessed, and EGFR-TKI therapy combined with WBRT is increasingly used in clinical practice. However, there has been no relevant report on the pseudoprogression of intracranial lesions from the patients accepting EGFR-TKI treatment combined with radiotherapy till now. Nevertheless, the efficacy and prognosis of a patient with pulmonary adenocarcinoma who received WBRT combined with EGFR-TKI targeted therapy and then presented with pseudoprogression is to be introduced in this paper. This patient was initially diagnosed with left lung adenocarcinoma stage IV (brain metastasis). Because EGFR gene mutation was positive, first-line targeted therapy of gefitinib combined WBRT were given at the same time. First-line efficacy was partial response (PR). After 8 months, the patient developed with bone metastasis. Considering the disease progression, the results of the genetic test again suggested that the T790M mutation was positive. Therefore, the second-line treatment was replaced to Osimertinib. After 7 months, the patient presented with pain in the right posterior occipital region, and the result of cranial MRI examination indicated that the right occipital metastasis was significantly larger than before. Then, the patient received resection of right occipital space occupying lesions, and the postoperative pathology indicated that no cancer in the brain tissue, but necrosis was seen. So pseudoprogression was considered.