Two major cap-binding components can drive mammalian translation initiation: the nuclear cap-binding complex (CBC) and eukaryotic translation initiation factor 4E (eIF4E). Although eIF4E-dependent translation has been well characterized, the mechanism of CBC-dependent translation remains unclear. Here, we demonstrate the previously unappreciated role of eIF4AIII in CBC-dependent translation. eIF4AIII is traditionally considered a component of the exon junction complex loaded onto mRNAs after splicing. In addition, we found that eIF4AIII can be recruited to the 5′-end of CBC-associated mRNA and promotes the translation of CBC-associated mRNA by helping to unwind secondary structures in 5′UTR. Therefore, our data provide evidence that eIF4AIII is a translation initiation factor specifically required for translation of CBC-associated mRNAs.