DDX3 is a prime target for viral manipulation,and it has multiple functions in viral infection,gene regulation and tumorigenesis.However,DDX3 functions in cervical cancer are unclear up to now.In our study,we focused on the connections between DDX3 and HPV infection to discover DDX3 roles in cervical carcinogenesis.We found that the expression of DDX3 and p21,a cell cycle-relative protein regulated by DDX3,is markedly decreased in HPV-positive cervical cancer cells compared with HPV-negative C33A cells.Correspondingly the overexpression of DDX3 in HeLa and SiHa cells improved p21 expression,and inhibited cell cycle progression from G1 phase to enter S phase,which decreased the virus infection of HPV16/18 E6.While the knockdown of DDX3 by siRNA treatment resulted in a decrease of p21 expression,and cell cycle was progressed from the G1 to S phase,as well as cell proliferation was improved.Furthermore we compared the relative expression level of DDX3 in 42 cervical cancer tissues and 18 noncancerous cervix tissues by immunohistochemistry.In cervical cancer tissues,DDX3 expression was much downregulated than the noncancerous cervix tissues.And DDX3 protein expression was associated with HPV infection and cancer differentiation.Our results indicated that DDX3 is decreased in HPV-infected cervical cancer cells and tissues,and the protein expression level is negatively correlated with HPV infection and the differentiated degree of cervical cancer.DDX3 is a novel potential biomarker for HPVpositive cervical cancer.