Frostbite injuries, often associated with exposure to extreme cold during outdoor activities, have been reported in the literature. However, few cases of frostbite caused by liquid oxygen have been documented. We report a 53-year-old man who was exposed to a liquid oxygen leak at work that caused severe frostbite injury to both hands. Early wound debridement and split-thickness skin graft for wound coverage were performed on day 8 after the frostbite injury. A second skin graft surgery was performed because of a failure of a patch of skin graft over the first web space of the left hand 20 days after the initial procedure. This unusual case of frostbite injury of the hands caused by liquid oxygen may help elucidate the characteristics of progressive deep-tissue injury that may lead to inadequate wound debridement and subsequent contracture scar formation over the web spaces of the hands despite early surgical treatment, which may impair hand function and lengthen hospitalization. Accurate clinical evaluation followed by early surgical wound management and the release of the web spaces of the hand with frostbite involvement may be beneficial in the treatment of deep hand frostbite injury.