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Zeli Huang,1,* Bojin Su,2,* Fang Liu,3,* Ning Zhang,1 Yilong Ye,4 Yang Zhang,1 Zhenghe Zhen,1 Shaoqiang Liang,1 Shaobo Liang,1 Lushi Chen,1 Weijun Luo,1 François X Claret,5,6 Ying Huang,7,8 Tao Xu1 1Department of Radiation Oncology, Cancer Center, First People’s Hospital of Foshan, Foshan 528000, Guangdong Province, People’s Republic of China; 2Department of Pathology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, People’s Republic of China; 3Department of Pathology, First People’s Hospital of Foshan, Foshan 528000, Guangdong Province, People’s Republic of China; 4Department of Infection, First People’s Hospital of Foshan, Foshan 528000, Guangdong Province, People’s Republic of China; 5Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; 6Experimental Therapeutics Academic Program and Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA; 7Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, People’s Republic of China; 8State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying HuangDepartment of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, People’s Republic of ChinaEmail huangying@sysucc.org.cnTao XuDepartment of Radiation Oncology, Cancer Center, First People’s Hospital of Foshan, Foshan 528000, Guangdong Province, People’s Republic of ChinaEmail asian.you@163.comIntroduction: Nasopharyngeal carcinoma (NPC) patients with HBsAg (+) commonly present with high frequencies of distant metastasis and poor survival rate; however, the mechanism has not been elucidated.Materials and Methods: We analyzed the yes-associated protein 1(YAP1) expression between HBsAg (+) and HBsAg (-) of NPC patients, then analyzed the relationship of YAP1 with survival. We further explored the anti-tumor role in NPC cell lines using YAP1 siRNA technique, and checked whether YAP1 regulatesepithelial–mesenchymal transition( EMT). The relationship between HBV X protein (HBx) and YAP1 was also tested using Dual-Luciferase reporter assay. Finally, we explored anti-YAP1 to inhibit tumor metastasis using the xenograft mice model.Results: In the current study, we found that YAP1 expression was higher in HBsAg (+) samples than in the HBsAg (-) samples, as a clinical signature, suggesting that YAP1 could be used as a prognostic factor for NPC. Our results showed that the HBx could regulate YAP1, further promoting cellular invasiveness through EMT. Anti-YAP1 can also decrease metastasis in vivo.Conclusion: Our findings suggest that YAP1 is a promising prognostic factor in NPC and could be used as a potential treatment target for NPC with HBV infection.Keywords: YAP1, hepatitis B, HBx, nasopharyngeal carcinoma, metastasis