Ultraviolet (UV) light is main carcinogen involved in the formation of skin cancer. UV radiation is a potent inducer of TNFα and cytokine gene expression in human keratinocytes. TNFα plays an important pro-inflammatory role in the skin, and is cleaved from its precursor by the action of Tumor Necrosis Factor α Converting Enzyme (TACE). TACE is cleaved from its preproform by furin, a proprotein convertase. The effect UV radiation has on the intracellular signalling pathways and that of furin’s expression and/or activity in keratinocytes is not known. The major signalling pathways activated by UV radiation are p38 MAPK, JNK and NF-κB. We investigated the effect 1 MED UV radiation [UVA (40 KJ/m2), UVB (2 KJ/m2) and UVAB (40+2 KJ/m2)] had on the expression of p-p38, p-JNK, NFκB as well as the activity of furin, and secretion of TNFα were examined using human primary keratinocytes (HEK), immortalised HaCaT cells as well as the squamous cell carcinoma Colo16 cell line. Colo 16 cells were more sensitive to high dose UVB and UVAB radiation than were HaCaT or HEK cells, though neither cell line was sensitive to UVA radiation. p38 MAPK was the major signalling pathway activated by UVA and/or UVB in all cell lines, though the level of activation differed. Only in the presence of IL1α did UVB and UVAB radiation induce maximal secretion of TNFα from HEK cells with lesser amounts secreted from the other cells. Of interest was that UV radiation increased furin expression in Colo16 and HaCaT cells which did not correspond to that of TNFα released from these cells. The differences observed between HaCaT cells and that of HEK cells raise questions about the use of these cells in studies on keratinocyte cell biology, the implications of which will be discussed.