HEADING AIMS: LncRNA HOXB-AS3 is proved as an oncogene in tumors. Herein, we determine the function and mechanism of HOXB-AS3 in epithelial ovarian cancer (EOC) cells. MATERIALS AND METHODS: Chi-square test, Kaplan-Meier (KM) analysis and Cox regression analysis were used to analyze the clinicopathological features of HOXB-AS3 in EOC patients. CCK8, transwell and wound healing assay were used to test the function of HOXB-AS3. Luciferase reporter assay, western blot and glycolysis rate assay were used for further mechanistic studies. KEY FINDINGS: HOXB-AS3 was abundantly expressed in EOC tissues, and higher levels of HOXB-AS3 in EOC patients were significantly associated with disease status and overall survival status. EOC patients with high levels of HOXB-AS3 had strikingly shorter disease-free survival (DFS) and overall survival (OS) times than those with low levels. HOXB-AS3 also might as an independent prognostic factor. Further study revealed knockdown of HOXB-AS3 significantly inhibited the proliferation, invasion and migration of EOC cells. Mechanistic investigations suggested that knockdown of HOXB-AS3 could decrease lactate dehydrogenase A (LDHA) expression and the extracellular acidification rate (ECAR) by sponging miR-378a-3p. SIGNIFICANCE: To our knowledge, this is the first study to suggest that HOXB-AS3 could crosstalk with miRNA in the cytoplasm and alter glycolysis in cancer cells. Our results improve our understanding of the mechanism of HOXB-AS3 and suggest that HOXB-AS3 can act as a predictor of OS and a target for EOC therapies.