CHK2 knockdown mimicked HBX-induced resistance to the S-phase arrest-inducing agents, and CHK2 overexpression overcame the resistance caused by HBX overexpression, indicating that CHK2 might serve as a potential mediator of HBX-induced chemoresistance and its de-phosphorylation caused by HBX impaired the S-phase arrest via inhibiting the downstream P53-P21 pathway in DLBCL. The gene discussed is TP53; the disease is diffuse large B-cell lymphoma.