Objective To explore the molecular mechanism of E6 promoting the development of cervical cancer through LncRNA SENCR/MDK axis. Methods Cervical cancer Hela cells, primary culture, P3 monolayer cells were selected as the study objects. LncRNA SENCR, MDK and E6 overexpressing plasmids were transfected into Hela cells. Control group (cells were not treated), pcDNA-SENCR group (intracellular transfection of SENCR overexpressing plasmids) and pcDNA-MDK group (intracellular transfection of MDK overexpressing plasmids), pcDNA-SENCR+MDK group (intracellular transfection with SENCR and MDK overexpression plasmid) and pcDNA-E6 group (intracellular transfection with E6 overexpression plasmid) were constructed. Dual fluorescein gene assay system determined the targeting relationship between LncRNA SENCR, MDK and E6. The ability of cell proliferation, apoptosis, migration and angiogenesis was compared in all groups.Results LncRNA SENCR and MDK were overexpressed successfully in Hela cells. There was a targeted relationship between them, and the difference was statistically significant (P<0.05). Compared with the Control group, SENCR overexpression inhibited the proliferation activity, cloning and migration ability of Hela cells, promoted apoptosis, up-regulated Cleaved caspase-3 expression, and down-regulated Cyclin D1, VEGF, and Ephrin B2 expression. MDK overexpression promoted the proliferation activity, cloning and migration ability of Hela cells, inhibited apoptosis, down-regulated Cleaved caspase 3 expression, and up-regulated Cyclin D1, VEGF, and Ephrin B2 expression, with statistically significant differences (P<0.05). The mRNA 3 ′non-coding region of LncRNA SENCR predicted the E6 binding site, and there was a targeting relationship between the two (P<0.05). Compared with the Control group, overexpression of E6 could inhibit the expression of LncRNA SENCR. After SILencing of E6, the expression of LncRNA SENCR was up-regulated, and overexpression of LncRNA SENCR could down-regulate the expression of E6, with statistical significance (P<0.05). Conclusion HPVE6/LncRNA SENCR/MDK axis plays an important role in the occurrence and development of cervical cancer. HPVE6 promotes MDK expression through targeted inhibition of LncRNA SENCR activity, and enhances the proliferation, cloning, migration and angiogenesis of cervical cancer cells, thus promoting the development of cervical cancer