Background:　Esophageal　cancer　is　one　of　the　most　common　malignant　tumours　in　humans.　A　series　of　esophageal　cancer　cell　lines　are　accompanied　by　human　papilloma　virus　(HPV)　infection,　but　the　mechanism　behind　HPV　in　cancer　malignancy　is　not　clear.　Methods:　This　research　was　conducted　in　different　generations　of　HPV　E6E7　gene-induced　human　foetal　esophageal　epithelial　immortalised　cells　(Shantou　Human　Embryonic　Esophageal　Epithelial　cell　line;　SHEE);　the　RNA　sequencing　transcriptomic　analysis　was　performed　to　explore　the　mechanism　of　HPV　infection　in　these　cell　lines.　Results:　The　results　showed　that　there　are　9,990　differential　genes　in　late-stage　cells　compared　with　HPV18　E6E7-infected　early　foetal　esophageal　epithelial　immortalised　cells.　Among　these,　4,882　genes　are　upregulated,　and　5,108　genes　are　downregulated.　We　used　bioinformatics　to　analyze　the　expression　and　function　of　aberrantly　expressed　lncRNA,　miRNA,　mRNA　and　construct　the　competing　endogenous　RNA　(ceRNA)　network　and　protein　protein　interaction　(PPI)　network.　Conclusions:　we　predicted　TP53TG1　promotes　to　malignant　transformation　of　SHEEs　by　acting　as　a　ceRNA　to　competitively　bind　to　miR-6835　and　regulate　IGF2　expression.　We　also　predicted　IL6　serve　as　prognostic　biomarkers　and　therapy　target.　With　these　results　maybe　provides　new　insights　into　the　mechanisms　of　HPV　carcinogenesis　in　esophageal　cancer.