Herpes simplex virus type-1 (HSV-1) is a neurotropic pathogen of humans that establishes latent infection in the sensory ganglia innervating the site of primary infection. A number of genes control HSV-1 pathogenicity and latency. Open reading frame P (ORF P) is one of these genes that might have a role in latency and pathogenesis. A complication in the analysis of the role of ORF P in the HSV-1 life-cycle is an antisense overlapping gene, ICP34.5. ORF P is also deleted in ICP34.5 negative mutants and to date, no definite function is attributed to it. An approach to analyze the function of a viral gene such as ORF P is to determine if this gene interacts with any of the cellular and viral proteins both in vitro and in vivo. Therefore, in this work, using GST pulldown assay and Western-blotting, it was investigated that with which cellular and viral gene products ORF P interacts. Our results showed that ORF P interacted with Thymidine kinase (TK) and also with an unidentified cellular protein. Conclusively the results of these works to-gether suggest possible role for ORF P in both splicing and replication of HSV-1.