Long noncoding RNAs (lncRNAs) have been suggested as essential regulators in the cancer progression. LncRNA TUC338 was found to promote the malignancy of various cancers, however, the involvement of TUC338 in nasopharyngeal cancer (NPC) has not been well characterized. Here, our results found the significant overexpression of TUC338 in NPC tissues. Higher level of TUC338 was also observed in NPC cells. Interestingly, NPC patients harboring overexpressed TUC338 have worse prognosis. Functional study indicated that down-regulated TUC338 remarkably suppressed the NPC cell proliferation and cell migration. Notably, depletion of TUC338 significantly inhibited the in vivo tumor growth. Mechanistically, TUC338 acted as molecular sponge of miR-1226-3p and attenuated the negative regulation of miR-1226-3p on the expression of fibroblast growth factor 2 (FGF2). Down-regulation of TUC338 inhibited FGF2 expression in NPC cells and tumor tissues. Overexpression of FGF2 attenuated the suppressed NPC proliferation upon the depletion of TUC338. Our results demonstrated the novel function of TUC338/miR-1226-3p/FGF2 axis in NPC progression, suggesting the potential diagnosis and therapeutics significance of TUC338 in NPC.