In clinical practice, regional chemotherapy of the liver applied as ‘hepatic arterial infusion’ (HAI) is often limited by device dysfunction or hepatic arterial obstruction. We report the case of a patient with mixed hepato/cholangiocellular carcinoma in which HAI with folinic acid (FA) and 5-fluorouracil (5-FU) was continued after thrombotic occlusion of the A. hepatica, resulting in a flow of drugs into the V. portae (via A. lienalis and V. lienalis). By using this ‘spleno-portal’ access for further chemotherapy with FA/5-FU, long-term control of the patient's disease was achieved. Analyzing our experience with this and three other patients with hepatic arterial thrombosis in which we continued HAI, a total of 33 regional treatment courses were applied, containing 5-FU/FA, mitomycin C, doxorubicin or combinations of these drugs. No unexpected toxicities were observed. In addition, the clinical course of three of those four patients strongly suggests the effectiveness of this approach. Thus, our results indicate that thrombosis of the A. hepatica does not necessarily have to result in an interruption of HAI. Continuation of regional chemotherapy despite hepatic arterial occlusion preserved control of intrahepatic tumor manifestations in patients who previously responded to regular HAI.