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Introduction Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. Material and methods From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. Result Twenty-one patients (F = 11, M = 10; age range 40–75 years, mean = 58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary ( n = 10) and non-colorectal primaries ( n = 8), and primary liver tumours ( n = 3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9 GBq (range 1.2–2.5 GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks ( p = 0.01). The mean pre-treatment SUV was 12.2 ± 3.7 and the mean post-treatment SUV was 9.3 ± 3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127 ± 115 vs 75 ± 72 μ/l, p = 0.39). Complications were seen in 4 patients (19%) including radiation hepatitis ( n = 2), cholecystitis ( n = 1) and duodenal ulceration ( n = 1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). Conclusion SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres.