We incubated AuNPs with normal and malignant Tanshinone-I ovarian cell lysates using positively and negatively charged AuNPs. In this study, we established HDGF as a possible therapeutic target for ovarian cancer by use of proteomic analysis and expression levels in cancer cells. This approach was validated through inhibition of cell proliferation upon silencing this factor by siRNA. Taken together, we show that this technique can be used to identify and validate new therapeutic targets for ovarian cancer, providing a generalized strategy for potential use in other diseases. Ovarian cancer is the most common malignancy of the female genital tract and one of the most lethal, essentially because there are currently no early screening or diagnostic tests for this disease. As a result, the cancer often remains clinically undetected until the later stages of the disease. Even though patients respond initially to chemotherapy after surgical Puerarin debulking, most of them develop terminal drug-resistant relapse. Hence, new therapeutic strategies, and thus new targets, are urgently needed to combat ovarian cancer. Identifying constituents of the protein corona that is formed when metal nanoparticles are incubated with cell lysates by using a combination of proteomics, bioinformatics, and nanotechnology could provide useful information regarding the development of the disease and allow us to discover new therapeutic targets in ovarian cancer, as well as potentially for other cancers in the future. Quantitative proteomics has allowed researchers to study protein populations found in tissues or biofluids. One technique used to study these protein sets is mass spectrometry, a detection tool with the ability to screen for myriad of proteins. In general, mass spectrometry-based proteomics is used to interpret the information encoded from genomes. Protein analysis by mass spectrometry has been fairly reliable when applied to small sets of protein samples. However, low-abundance proteins may escape detection using these general methodologies due to the Vroman effect, in which highly mobile proteins that adsorb onto surfaces are replaced by less mobile proteins. In the present study, we were able to differentially detect proteins not observed in the cell lysates using conventional methods. In our strategy, these low abundance proteins were enriched by selective interaction with the modified surface of gold nanoparticles. The different proteins that adsorb onto the surface of the nanoparticle are reflected in protein corona light-scattering behavior, charge, and proteomics. These results clearly suggest that tuning the surface charge of engineered nanoparticles can modulate the formation of protein corona around them. Such modulation is important to detect lowabundance proteins in order to identify new therapeutic targets.