Alpha interferon (α-IFN) is used for the treatment of various systemic disorders. Side-effects of α-IFN therapy can involve numerous organ systems, but sudden hearing loss has only once been recorded. We report a case of sudden hearing loss occurring in a patient with chronic hepatitis C treated with α-IFN and recovered five days after the discontinuation of this agent. This is the first record of anti-endothelial cell antibodies detection in a patient with sudden hearing loss. The finding of anti-endothelial cell antibodies suggests an association between sudden hearing loss and microvascular damage during interferon therapy.