Currently, sorafenib is the only systemic therapy capable to increase the overall survival of the patient affected by advanced hepatocellular carcinoma. Unfortunately, its side effects limit the therapeutic response. Superparamagnetic iron oxide nanoparticles (SPIONs) are very attractive for drug delivery as they can be targeted to specific sites in the body through the application of a magnetic field, thus improving intracellular accumulation and reducing adverse effects. Here, nanoformulations based on polyethylene glycol modified phospholipid micelles, loaded with both SPIONs and sorafenib, were successfully prepared and thoroughly investigated by means of complementary techniques. The nanovectors resulted effective drug delivery systems with good stability in aqueous medium and controlled drug loading. An in vitro system was specifically designed to prove that the SPION/Micelles can be efficiently held by using magnetic field under the flow conditions typically found in the human liver. Human hepatocellular carcinoma (HepG2) cells were selected as in vitro system to evaluate the tumor cell targeting efficacy of the superparamagnetic micelles loaded with sorafenib. The experiments demonstrated that the delivery platform is able to enhance the drug antitumor effectiveness when magnetically targeted. The presented magnetic nanovectors represent promising candidates for the targeting of specific hepatic tumor sites, where the selective release of sorafenib can improve its efficacy and safety profile.