Nasopharyngeal carcinoma (NPC) is a kind of head and neck cancer with a characteristic regional distribution. Increasing evidence has illustrated that long noncoding RNAs (lncRNAs) exert the regulatory function in tumor development. Nevertheless, the specific functions of lncRNA HOXA10 antisense RNA (HOXA10-AS) in NPC remain to be clarified. In this research, quantitative reverse transcription polymerase chain reaction detected HOXA10-AS expression in NPC cells. Cell counting kit-8, colony formation, and transwell assays were utilized to measure the proliferation and migration of NPC cells. Moreover, mechanism assays detected the interaction of different genes. Briefly, HOXA10-AS was highly expressed in NPC cells. HOXA10-AS down-regulation restrained NPC cell proliferation and migration. Further, HOXA10-AS could bind to miR-582-3p by acting as a competing endogenous RNA. Besides, Ras-related protein Rab-31 (RAB31) was proven as the target gene of miR-582-3p. Additionally, E2F transcription factor 1 (E2F1) acted as a transcription factor to activate HOXA10-AS expression. In the final rescue assays, we observed that the effect of HOXA10-AS depletion on NPC cell growth could be fully reversed by RAB31 overexpression or miR-582-3p inhibition. In short, our research proved that HOXA10-AS activated by E2F1 facilitated proliferation and migration of NPC cells through sponging miR-582-3p to upregulate RAB31.