The aim of the present study was to determine the function of microRNA-153 (miR-153) in the viability of nasopharyngeal cancer (NPC) cells and determine the underlying molecular mechanism. The expression of miR-153 in patients with NPC was markedly decreased compared with that in paracarcinoma tissue. miR-153 upregulation observably decreased cell viability, induced apoptosis, increased caspase-3 and-9 activity, and increased the B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 protein expression ratio in 13-9B cells. miR-153 upregulation also suppressed transforming growth factor-β 2 (TGF-β 2) and Smad2 protein expression in 13-9B cells. TGF-β 2 inhibitor enhanced the effect of miR-153 upregulation on the inhibition of cell viability, induction of apoptosis, increase in caspase-3 and-9 activity, and increase in Bax/Bcl-2 protein expression ratio in 13-9B cells. The results of the present study indicate that miR-153 affects the progression of NPC by targeting the TGF-β 2 /Smad2 signaling pathway.