Confocal Raman Microscopy (CRM) is used to study the cell internalization of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) fabricated by emulsion techniques with either poly(ethylene imine) (PEI) or bovine serum albumin (BSA) as surface stabilizers. HepG2 cells were exposed to PEI and BSA stabilized PLGA NPs. Spontaneous Confocal Raman Spectra taken in one and the same spot of exposed cells showed bands arising from the cellular environment as well as bands characteristic for PLGA, proving that the PLGA NPs have been internalized. It was found that PLGA NPs preferentially colocalize with lipid bodies. The results from Raman spectroscopy are compared with flow cytometry and confocal scanning laser microscopy (CLSM) data. The advantages of CRM as a label-free technique over flow cytometry and CLSM are discussed. Additionally, cell viability studies by means of quick cell counting solution and MTT tests in several cell lines show a generally low toxicity for both PEI and BSA stabilized PLGA NPs, with BSA stabilized PLGA NPs having an even lower toxicity than PEI stabilized.