The differential diagnosis of progression and pseudoprogression is one difficulty in current immunotherapy. Since the time point and criteria for pseudoprogression diagnosis are not yet unified, current diagnosis and treatment rely on imaging and pathology. Here we report a 57-year-old Chinese male presented solitary left lower lung nodule with enlarged left hilar and mediastinal lymph nodes. Bilateral adrenal nodules and bilateral parietal lobe nodules were identified. The nodules were considered malignant by CT or MRI examinations. The patient was diagnosed left lower peripheral lung cancer with left hilar and mediastinal lymph node metastasis, bilateral adrenal metastasis, and bilateral parietal lobe metastasis. Progression was observed after the first-line pemetrexed + cisplatin (PP) standard chemotherapy. Due to the identification of strong positive PD-L1 expression (90%) in primary tissue immunohistochemistry, second-line IBI308 (sintilimab) immunotherapy was implemented. After the third cycle of immunotherapy, partial response was observed with the left lung lesion and the lung hilus and adrenal metastases, while pseudoprogression was found at the left lung and right hepatic lobe, and rare gingival progression was also identified. Palliative surgery was performed to remove the gingival metastatic lesion. The lesions of the lung, hilar and mediastinal lymph nodes and adrenal gland responded well, but the patient died due to uncontrollable progression of metastatic lesions in the brain. Whole-exome sequencing on gingival metastasis revealed pathogenic mutations in several important driver genes, including TP53, ErbB2, MET and PTEN. This study reported the coexistence of primary lesion response, pseudoprogression and progression in immunotherapy in lung cancer patient with rare gingival metastasis, and provided experience for handling mixed responses in immunotherapy.