Hyaluronic acid (HA) is now extensively employed for esthetic concerns. In the majority of cases, HA is considered to be safe, but mild-to-severe complications can occur in a few cases. Hyaluronidase is enzymes that degrade HA, also being suggested for the treatment of HA filler-induced complications. However, hyaluronidase has been reported to be a potential cause of allergic responses in some anesthetic and ophthalmic literature. However, there are few reports of allergic reactions to hyaluronidase in cosmetic medicine. We herein report on a 39-year-old Asian woman who developed a delayed allergic hypersensitivity to hyaluronidase in the treatment process of HA-related granulomatous reaction.