Gastric cancer is one of the most common human tumors worldwide. The biggest bottleneck is a lack of advanced and sensitive protocols for the diagnosis of patients with early-stage gastric cancer. Therefore, more sensitive methods of diagnosing gastric cancer are urgently required to improve survival rates. In this clinical study, contrast-enhanced computed tomography (CECT) with targeting nanoparticles contrast agent (CECT-TNCA) was used to diagnose early-stage gastric cancer. The specific-targeted tyrosine kinase inhibitors of gastric cancer, including platelet-derived growth factor receptor-β, Ret and Kit, were used as TNCAs. A total of 484 patients with suspected gastric cancer were voluntarily recruited to investigate the efficacy of CECT-TNCA in the diagnosis of patients with early-stage gastric cancer. Patients with suspected gastric cancer were subjected CT and CECT-TNCA to detect whether gastric tumors existed. TNCA was orally administered before CT and CECT-TNCA (20 min). Our diagnostic data revealed that CECT-TNCA improved sensitivity and provided a new protocol to diagnose tumors in patients with suspected gastric cancer at the early stage. In addition, imaging using CECT-TNCA enabled the visualization of tiny nodules in the gastric area. CECT-TNCA diagnosed 182 patients with suspected gastric cancer as tumor-free. CECT-TNCA confirmed gastric cancer in 302 patients. Our novel diagnosis indicated significantly (P<0.01) differential signal enhancement in the gastric nodules via CECT-TNCA compared with CT, suggesting higher accuracy and the accumulation of TNCA in tumor nodules in the stomach. Furthermore, survival rates of patients detected by early-diagnosis of CECT-TNCA were significantly higher than the mean five-year survival (P<0.01). In conclusion, our investigations demonstrate that the sensibility and accuracy of CT is improved through combination with liposome-encapsulated nanoparticle contrast agent for the diagnosis of early stage gastric cancer when compared with single CT detection. CECT-TNCA improves the accuracy of CT and diagnostic confidence in assessing mural enhancement in patients with suspected gastric cancer.