Hepatocellular carcinoma remains one of the most common malignant tumors in the world. Newcastle disease virus (NDV) has been proved to be an efficient oncolytic agent. NDV tumor killing efficacy is not only dependening on the NDV strain but the type of tumor targeted. It is significant to discover more effective and safe oncolytic strains. We investigated the effectiveness of genetically engineered NDV Anhinga strain in hepatoma treatment. The modified virus containing an insertion of enhanced green fluorescent protein (EGFP), named NDV/Anh-EGFP. The antitumor efficacy of the recombinant virus on hepatoma was examined both in vivo and in vitro. NDV Anhinga strain, which could be classified as a lytic strain, is an effective oncolytic agent on hepatoma. There was no significant difference in the TCID50 and growth capability between the recombinant NDV and the parental. NDV/Anh-EGFP can obviously inhibit hepatocarcinoma development in vitro and in vivo. We demonstrate Anhinga strain could become a potent candidate for clinical carcinoma therapy especially for hepatocarcinoma.