Human papillomaviruses (HPVs) of genus beta appear to be involved in the early stages of skin cancer development because both the prevalence and viral load are higher in precancerous actinic keratoses than in skin cancers. IL-8 is an inflammatory cytokine, which serves to alert the surrounding tissue after UV-induced damage. We examined the effects of the E2, E6 and E7 proteins of HPV8 and the E6 proteins of various HPV genotypes on IL-8 secretion from primary keratinocytes. HPV5 and HPV8 E6 showed the highest downregulation of basal IL-8 secretion. HPV8-E6 also negatively modulated IL-8 mRNA expression and protein secretion upon UVB irradiation. The downregulation of IL-8 in actinic keratoses may weaken the response to UV-induced damage and thus favour the accumulation of UVB induced mutations.