OBJECTIVE: This study attempted to investigate the expression and significance of lncRNA HOST2 (human ovarian cancer- specific transcript 2) and microRNA let-7b in human papillomavirus (HPV)-positive cervical cancer (CC) tissues and cell lines. PATIENTS AND METHODS: The expression of levels of HOST2 and let-7b were detected by qRT-PCR in HPV-positive CC tissues and cell lines. The HPV-positive CaSki and HeLa cells were divided into the Blank, NC, pcDNA3.0-HOST2, siHOST2, let-7b mimic, and pcDNA3.0-HOST2+ let7b mimic groups. Dual-luciferase reporter gene assay was employed to verify the targeting relationship between HOST2 and let-7b, MTT and flow cytometry to determinate cell proliferation and apoptosis, and wound-healing and transwell assays to evaluate cell migration and invasion capabilities. RESULTS: HOST2 was up-regulated but let-7b was down-regulated in HPV-positive CC tissues and cells. Dual-luciferase reporter gene assay confirmed the targeting relationship between HOST2 and let-7b. Over-expressed HOST2 reduced let-7b expression, promoted proliferation migration and invasion and inhibited the apoptosis of CaSki and HeLa cells; however, silencing HOST2 or overexpressing let-7b enhanced the expression of let-7b, inhibited proliferation migration and invasion, and promoted the apoptosis of CaSki and HeLa cells, and let-7b mimic could reverse the promoting effect of HOST2 on the growth of CC cells. CONCLUSIONS: HOST2 was upregulated in HPV-positive CC tissues and cells, which could promote the proliferation, migration and invasion, but inhibit the apoptosis of HPV-positive CC cells via inhibition of let-7b.