RNA interference is the process that double-stranded RNA induces the homology-dependent degradation of cognate mRNA mediated by 21-23 nucleotide short interfering RNA (siRNA). Here, we describe a simple virus vector for efficient delivery of siRNA into mammalian cells utilizing the well-defined H1-RNA promoter and conventional adenovirus. In this pilot study, p53 was targeted by this vector. Our results demonstrate efficient and specific knock-down of p53 in breast cancer MCF-7 and lung carcinoma A549 cells and indicate a prospective application of this siRNA expressing recombinant adenovirus system in functional genomics, cancer gene therapy and virus inhibition.