〔Abstract〕 Objective To explore the role and molecular mechanism of circHIPK3 in the migration and invasion of nasopharyngeal carcinoma cells. Methods Firstly, we searched public databases and analyzed the expression level of circHIPK3 in nasopharyngeal carcinoma tissues and non-cancerous tissues in Gene Expression Database(GEO).Then, the circHIPK3 siRNA was synthesized and transfected into the NPC cell line 5-8F. After validate the efficiency of circHIPK3 knockdown, the proliferation, migration and invasion capacities of 5-8F cells were evaluated by CCK-8, wound healing and transwell assay. Meanwhile, the mRNA and protein expression of downstream genes, includingCDH1,CDH2,MMP2,MMP9andIL-6/STAT3were determined by RT-qPCR and Western blot. Finally, transcriptome sequencing technology was used to analyze the significantly differentially expressed genes after the interference of circHIPK3-siRNA in 5-8F cells, in order to find out the key genes mediating the oncogenesis role of circHIPK3. Results circHIPK3 expression significantly increased in nasopharyngeal carcinoma tissues compared with non-cancerous tissues(P<0.05).After siRNA-specific knockdown of circHIPK3 expression in 5-8F cells, the proliferation, scratch healing rate, and the number of migrated/invaded cells were significantly reduced(P<0.05,P<0.01,P<0.05 respectively). Meanwhile, the mRNA and protein levels ofCDH1significantly increased(P<0.001), but theCDH2,MMP2,MMP9,IL-6/STAT3mRNA and protein levels were significantly reduced(P<0.05). Further analysis by RNA-seq showed that the expression of AL645922.1, SCO2, AL136295.1 and ISY1-RAB43 was significantly up-regulated(P<0.05), and the expression of BIVM-ERCC5, FAM47E-STBD1, INO80B-WBP1, NAIP, C15orf38-AP3S2, BCL2L2-PABPN1 and SMIM11B was significantly down-regulated(P<0.05) in circHIPK3-siRNA transfected 5-8F cells. Conclusion circHIPK3 expression is significantly upregulated in nasopharyngeal carcinoma tissues. circHIPK3 promotes 5-8F cells proliferation, migration and invasion by regulating the expression of E-Cadherin, N-Cadherin, MMP2, MMP9 and IL-6/STAT3. Genes such as AL645922.1 and BIVM-ERCC5 may play a key role in promoting the migration and invasion of nasopharyngeal carcinoma 5-8F cells mediated by circHIPK3.