Long non-coding RNA homeobox A11-antisense RNA (HOXA11-AS) has been implicated in cisplatin (DDP) resistance in multiple types of cancer. The purpose of the present study was to investigate the role of HOXA11-AS in DDP-resistant nasopharyngeal carcinoma (NPC) cells. The expression levels of HOXA11-AS were examined using reverse transcription-quantitative PCR. Cell viability was measured using a Cell Counting Kit-8 assay, and a TUNEL assay was utilized to assess cell apoptosis. The expression levels of apoptosis-related factors (Bax and Bcl-2) were detected by western blot analysis. The interaction between microRNA-98 (miR-98) and HOXA11-AS or pre-B-cell leukemia homeobox 3 (PBX3) was demonstrated using bioinformatics analysis, dual-luciferase reporter assays and RNA immunoprecipitation assays. HOXA11-AS and PBX3 expressions levels were upregulated, whereas miR-98 levels were downregulated in DDP-resistant NPC tissues. Patients with NPC with high HOXA11-AS expression had a low survival rate. Knockdown of HOXA11-AS enhanced the DDP sensitivity of DDP-resistant NPC (5-8F/DDP and SUNE1/DDP) cells, which was demonstrated by the accelerated apoptosis. In addition, HOXA11-AS inhibited the expression levels of miR-98 through direct interaction. Furthermore, miR-98 inhibition counteracted the inductive effect of HOXA11-AS-knockdown on the DDP sensitivity of NPC cells. PBX3 was a target of miR-98 and was positively modulated by HOXA11-AS. Overexpression of PBX3 reversed the suppressive effect of HOXA11-AS silencing on the DDP resistance of NPC cells. The data demonstrated that HOXA11-AS enhanced DDP resistance in NPC via the miR-98/PBX3 axis, providing a potential therapeutic target for patients with DDP-resistant NPC.