Non-small-cell lung carcinoma (NSCLC), major lung cancer is currently considered one of the leading causes of mortality and has become a progressively serious global public health burden. However, the conventional drug delivery approaches were unable to efficiently inhibit the proliferation and metastasis of lung cancer cells. Exploiting Nanobubbles (NBs) as a novel drug delivery system has recently a research hotspot mainly due to their outstanding characteristics such as small size, biosafety and competent drug-transporting ability. The present study aimed to establish a novel biocompatible approach for Nanobubble constructions by the water-in-oil method and loading quercetin inside the obtained micelles. Dextran coating was used for more stability of NBs and the effectiveness of drug delivery to A549 NSCLC and HeLa cells was evaluated. Ultrasound waves were used to stimulate the Nano bubble to release the drug. The approximate size of NBs was 0.149 nm that reach by dynamic light scattering dominantly with a spherical shape visualized by TEM. Excellent drug-loading capacity and ultrasound-mediated release of quercetin were confirmed by a UV spectrophotometer with an absorption of about 1.6. NBs efficiently inhibited the proliferation of NSCLC cells in a concentration-dependent manner as well as the capability to achieve ultrasound enhancement. This experiment showed that obtained NBs effectively delivered quercetin into lung cancer cells promoted by ultrasound irradiation. In conclusion, proposed biocompatible quercetin-loaded NBs are suitable for ultrasound-targeted drug delivery and are thus a promising strategy for their noninvasive clinical application.