 Hepatic intra-arterial chemoembolization TACE is proposed when potentially curative therapy eg. surgical resection, percutaneous ablationis no longer possible. Prospective and non-randomized retrospective studies showed TACE to be capable to increase survival vs controls. In 2002 the first results of two RCTs were published which had been conducted on unresectable HCC patients, designed to assess the impact produced by TACE on survival, demonstrated a statistically significant advantage in TACE treated patients compared to controls. The same results have been confirmed by a meta-analysis conducted on 14 trials published in literature. The limitations of TACE are represented however by the difficulties in obtaining a complete necrosis of the lesion treated and for this reason new embolization agents are being developed to increase the efficacy of TACE in HCC as the microsphere, in poly vinyl alcohol and co-acrylic acid that are not reabsorbable and induce permanent embolization. The first experimental studies using microsphere showed the good tolerability and the higher rate of tumor necrosis, but no RCTs have been conducted to investigate their impact on survival. Objectives. The primary aim of this study is to compare 2 years survival of patients randomized to selective traditional TACE or selective TACE via microspheres loaded with Doxorubicin. Secondary objectives investigate the time to progression of disease radiologic and symptomatic by radiologic, laboratory tests and the QoL questionnaire administration. Methods. This is a multicentre, randomized, open-label, active controlled study in HCC patients treated with standard TACE vs TACE with doxorubicin - loaded microsphere. The study comprises a selection period, a treatment period and a follow up phase with a total duration of 2 years from randomization. Expected results. The sample sizealfa 5, power 80 is adequate to detect a 20 difference between TACE with microsphere vs traditional TACE. 