The present invention relates to the inhibition of Hepatitis B virus (HBV) replication by RNA molecules of the present invention. Specifically, the RNA molecules of the present invention are double-stranded ribonucleic acid molecules (dsRNA). Specifically, the invention relates to small interfering RNAs (siRNA) which are double-stranded RNAs that direct the sequence-specific degradation of messenger RNA in mammalian cells. The invention relates to development of a new anti-HBV therapy by inhibition of Hepatitis B Virus (HBV) replication using stably-expressed short hairpin RNAs (shRNA), which degrade HBV pregenomic RNA and message RNAs. Included are methods of treatment of cancer by the administration of RNA molecules of the present invention in combination with surgery, alone or in further combination with standard and experimental chemotherapies, hormonal therapies, biological therapies/immunotherapies and/or radiation therapies.