Non-small cell lung cancer (NSCLC) initiates in the non-small cells of the lung and is one of the most common types of human cancer. It is known for its rapid growth, easy migration, invasion and reoccurrence, and has the highest incidence rate of all types of cancer. Early detection of NSCLC is difficult to achieve and this is the primary reason for low survival rates in NSCLC. Contrast-enhanced ultrasound is the most common application for evaluating patients diagnosed with NSCLC. In the present study, a contrast-enhanced ultrasound combined with nanoparticles was performed with the aim of identifying patients with NSCLC at an early stage. The present study evaluated the effectiveness of administering a nanoparticle contrast agent through respiration in combination with enhanced ultrasound at improving image quality compared with traditional ultrasound. This maybe a novel method of detecting early-stage tumors in patients. There are numerous benefits to conducting diagnoses of NSCLC using contrast-enhanced ultrasound. It is a non-invasive imaging modality, induces little pain, has a low cost, an extensive range and produces high-resolution images. This means that it is safer and more beneficial to use in patients with NSCLC than conventional imaging examinations, including X-ray and bronchoscopy. Furthermore, the nanoscale microbubble contrast agent containing liposome-encapsulated epidermal growth factor receptor was inhaled by nebulization, which may lead to an enhanced ultrasound image. The sensitivity of contrast-enhanced ultrasound was investigated in mice with early stage NSCLC. The results indicated that ultrasound administrated with nanoscale microbubble enhanced sensitivity and improved image quality compared with simple ultrasound. Furthermore, enhanced ultrasound resulted in a reliable and sensitive assessment of tumor mass in early-stage tumors. Altogether, contrast-enhanced ultrasound facilitated the efficient detection of NSCLC in patients at an early stage. This protocol improved the understanding of the pathophysiology of NSCLC and may be applied in the detection of early-stage tumors in patients suspected of having cancer.