Plasma hyaluronan-binding protein (PHBP) is a serine protease implicated in proteolysis under inflammatory conditions. We identified laccaic acid, a widely used food coloring from scale insects, as a potent inhibitor of the protease in terms of both autoactivation of the PHBP proenzyme (IC(50) = 0.35-0.55 µg/ml) and the catalytic activity of the active enzyme (IC(50) = 1.1 µg/ml).