In in vivo study with LLC allograft bearing mice, treatment of thiacremonone significantly inhibited tumor growth by approximately 50–60%. The immunohistochemistry analysis of tumor section by H&E, and by proliferation antigens against PCNA staining revealed that thiacremonone inhibited tumor growth. In addition, our data also showed that thiacremonone inhibited expression of PRDX6 accompanied with inhibition of glutathione peroxidase activity in lung tumor tissues. Moreover, expression of proapoptotic proteins, cleaved form of caspase-3 and Bax, was increased and anti-apoptotic protein, but expression of Bcl2, cIAP, and xIAP was decreased by treatment of thiacremonone. Our results showed that thiacremonone showed no cytotoxic effect in the normal CCD-18 Co colon, and LL24 lung normal cells. These data suggest that thiacremonone may be potentially beneficial for anti-cancer effect with comparatively low toxicities via interaction with PRDX6. Hepatocellular carcinoma is one of the major cancers worldwide. HCC is especially common in Asia-Pacific countries and is ranked the fourth highest cause of death among cancers in Japan. Despite recent advances in resection and ablation techniques, the recurrence rate after initial treatment is high and prognosis is poorer than other carcinomas. Improved risk stratification and accurate individualized prediction of postoperative recurrence and survival can help guide patient counseling, follow-up scheduling, administration of adjuvant therapies, and design of clinical trials. Accumulating evidence has shown that not only genetic but also epigenetic changes play crucial roles in the genesis and prognosis of cancer. Global levels of several histone modifications, as well as histone modification enzymes, have clinical significance in several cancers. A recent review on histone modifications and cancer also referred its potential that serves as a biomarker. Previous studies in HCC demonstrated the clinical significance of individual histone methylation levels. High levels of tri-methylation of lysine 4 on histone H3 and trimethylation of lysine 27 on histone H3 correlated with aggressive features and poor prognosis. However, little is known about global histone acetylation levels in HCC. One immunohistochemical study revealed that the levels of acetylation of lysine 9 on histone 3 and acetylation of lysine 8 on histone 4 were higher in HCC than in non-cancerous liver, but the clinical significance remains unknown. In this study, we focused on acetylation of lysine 27 on histone H3 and its relation with H3K27me3. H3K27ac is an active enhancer marker and reflects global cell-type-specific gene expression in various cancer cell lines. H3K27me3 is another histone modification of the same site, and acts instead as a silencer. We evaluated both H3K27ac and H3K27me3 levels in HCC using specific monoclonal antibodies, and used digital slide scanner and image analyzing R428 software to quantify the results as objectively as possible. In addition, we examined nuclear localization of H3K27ac and H3K27me3 by double immunofluorescence in frozen sections.