OBJECTIVE : This study aimed to detect the expression of eukaryotic translation initiation factor 3 subunit a (eIF3a) in ameloblastoma (AB) tissues compared with normal oral mucosa (NOM) tissues and investigate the roles of eIF3a in the immortalized ameloblastoma cell line (AM-1) cell proliferation and apoptosis. METHODS : We performed immunohistochemistry to determine the expression of eIF3a in AB tissues (n = 83) and NOM tissues (n = 20). Real time-quantitative polymerase chain reaction and Western blot analyses were conducted with AB tissues (n = 30) and NOM tissues (n = 6). The correlation between eIF3a expression and the clinical/pathologic features of patients with AB is also presented. The functional role of eIF3a in AM-1 cells was assessed with lentiviral vector-mediated shRNA (small hairpin RNA). RESULTS : Our results indicated that eIF3a was significantly upregulated in AB. Additionally, eIF3a knockdown in AM-1 cells significantly inhibited cell proliferation and promoted apoptosis. CONCLUSIONS : These data indicate that eIF3a facilitates the survival of AB cells and may serve as a promising therapeutic target in AB.