Giant-cell carcinoma of the lung (GCCL) is a rare histological form of poorly differentiated non-small-cell lung cancer, which is classified as a subtype of pulmonary sarcomatoid carcinomas. In this case report, we describe the case of a 50-year-old Chinese male who presented with a pulmonary nodule in the right upper lobe of his lung. After thoracoscopic lobectomy, a histopathologic diagnosis of GCCL was made. He did well postoperatively, showing no local recurrence or distal disease in a 7-year follow-up period. Furthermore, for this case, we also analyzed 295 tumor-related driver genes with high-throughput sequencing technology. We found that treatment using MEK inhibitor, CDK 4/6 inhibitor, and TP53 inhibitor may provide a new therapeutic direction for GCCL. Therefore, complete tumor excision is the best choice of treatment strategy at the early stage of GCCL and gene target therapy may be a new therapeutic option for this disease.