We present here a case of extensive necrotizing fasciitis during sorafenib treatment in a patient with HBV-related hepatocellular carcinoma. Despite emergent extensive surgical debridement, the patient's clinical status progressive worsened until interruption of sorafenib therapy. The patient was successfully treated with temporal interruption of sorafenib therapy. To our knowledge, this is the first case report of sorafenib-associated necrotizing fasciitis. Given the life-threatening nature of the infection and the necessity for urgent intervention, clinicians should be aware of this possible adverse effect of tyrosine kinase inhibitors.