Lymphoma is not a common focus for viral therapy as many researchers do not consider lymphoma as a suitable target for viral vectors. In the present study, the infection, replication and cytotoxicity of herpes simplex virus (HSV) and adenovirus vectors were screened and evaluated in different lymphoma cell lines. Three recombinant viruses, BAC-HSV-1-eGFP, Adv-eGFP and an NV1020-like oncolytic HSV-1 virus strain named BAC-HSV-1-eGFP-delIRs, inserted with green fluorescent protein (GFP) as a reporter, were applied to evaluate the efficiency of viral infection and replication and cytotoxicity to lymphoma cells. Four types of lymphoma cell lines (SNK-6, Jurkat, Raji and Hut 78) were examined. We found that the HSV-1 vector, BAC-HSV-1-eGFP, was able to infect and replicate in the three lymphoma cell lines (Jurkat, Raji and Hut 78) and inhibit the growth of these cells more efficiently than adenovirus vector Adv-eGFP. The sensitivity of the four types of lymphoma cell lines to the viral vectors was different. The human cutaneous TL cell line Hut 78 was more sensitive to the viral vectors than the other cell lines. However, the human NK/T lymphoma cell line SNK-6 was not infected by any of the viral vectors and did not allow replication of the viruses. In conclusion, lymphoma may be a potential target for HSV-1 vector-mediated viral therapy.