Cytokines induce inflammatory and immune responses in tumors after photodynamic therapy (PDT). Since there are no reports of IL-6 in nasopharyngeal cancer (NPC) cells following PDT, we evaluated IL-6 expression in two different NPC tumors after hypericin mediated PDT. Interleukin-6 transcription was significantly upregulated in PDT-treated CNE-2 poorly differentiated cells but not in HK1 well differentiated cells. In vivo, IL-6 mRNA expression was elevated in PDT-treated CNE-2 tumors but not in HK1 tumors. In conclusion, the study elucidated that the cell type, degree of histological differentiation and the basal expression of the cytokine influence the cytokine response following PDT.