This study describes preparation and use of novel labeled and antibodious polymeric nanolabels (anti-alpha fetoprotein cross-linked nanolabels) as an immunogenic and semisynthetic nanolabel with potential prognostic and therapeutic roles for hepatoma cancer. Specificity, uptake, and binding efficiencies of the nanolabel have been examined in a human hepatosarcoma cell line HepG2, a human colorectal cell line DLD-1, and a mouse myoblast cell line C2. Labeling of the cells has been performed by treating live and fixed cells with varying concentrations of the nanolabels and then, the cells have been examined under a fluorescence microscope. In addition, all cell lines have also been labeled using FITC-conjugated nanotrastuzumab to compare the results obtained with those of the binding of the FITC-nanoanti-alpha fetoprotein nanolabels. Results show that FITC-conjugated anti-alpha fetoprotein cross-linked nanolabels have been taken up by both live and fixed cells and have efficiently and specifically labeled HepG2 cells at a quite low concentration. Taken all together, the results indicate that the novel targeted nanoimaging tools and technique demonstrated their ability to detect the distribution of the nanolabels as probes in hepatoma cells. (c) 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 472479, 2013