Non-coding RNAs are critical regulators of tumor biology. nc886, a recently identified non- coding RNA, is overexpressed in some tumors, but undetected in others. However, the precise role of nc886 remains unclear in cervical cancers. In this study, we found that nc886, major vault protein (MVP), and E2F1 exhibited coordinate expression as they were silenced in normal tissues but overexpressed in cervical cancer tissues. We subsequently demonstrate that nc886 upregulation was a critical response to chemotherapy treatment of cervical cancer cells. Mechanistically, inhibition of nc886 increased chemosensitivity, induced apoptosis, and suppressed the protein expression of MVP, a critical regulator of drug resistance. Furthermore, we identify E2F1 as a key transcription regulator of nc886 that directly interacts and modulates promoter activity. Taken together, we demonstrate that E2F1 sufficiently promotes nc886 transcription and in turn MVP expression to drive drug resistance in cervical cancer cells.