The chemotherapy of nonsmall cell lung cancer is making brilliant progress by introducing gefitinib, an oral tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR). Although the hepatotoxicity has often been encountered with gefitinib therapy, no standard remedies for this side effect are available. Our aim is to clarify the efficacy of Proheparum^®, a liver hydrolysate composite used to treat chronic hepatic diseases, on the hepatotoxicity resulting from gefitinib therapy. From November 2007 to May 2010, we reviewed patients with nonsmall cell lung cancer and identified 10 patients who developed Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 Grade 1 or more hepatotoxicity after the initiation of gefitinib therapy, followed by receiving Proheparum^®. The clinical effects of Proheparum^® were retrospectively investigated. Decreased serum alanine aminotransferase (ALT) levels were recognized in 8 of 10 patients, and decreased serum asparatate aminotransferase (AST) levels were recognized in 7 of 10 patients after the initiation of Proheparum^®. Among these 8 patients, 3 improved and showed decreased levels of serum ALT levels without interruptions or dose reductions of gefitinib administration. The remaining 5 patients were given Proheparum^® concomitant with dose reductions or interruptions of gefitinib, and/or administration of Stronger Neo-minophagen C^® (SNMC), a glycyrrhizin preparation. Three of these 5 patients were successfully readministered gefitinib together with Proheparum^® without relapse of hepatotoxicity. In conclusion, Proheparum^® may be effective for nonsmall lung cancer patients with hepatotoxicity as a result of gefitinib therapy.