Here, we initially observed CUL2 mRNA and protein expression and the correlation with HPV16 E7 expression in HPV16 positive cervical cancer and its precursor tissues, confirmed CUL2 potential role in clinic and function in cell growth in vitro and tumorigenicity in vivo, and then verified the existence of CUL2/E2F transcription factor 1 (E2F1)/miR-424 regulatory loop and its contribution to CUL2 overexpression in HPV16 positive cancer cells. This evidence concerns the gene CUL2 and cancer.