The present study aimed to explore the combined role of microRNA (miR)-34a, melanoma antigen-A (MAGE‑A) and p53 in altering the chemosensitivity of retinoblastoma (RB) cells. Human RB and adjacent tumor tissues, as well as human RB cell lines (HXO‑Rb44, SO‑Rb50, Y79 and WERI‑Rb-1) were used. In addition, four chemotherapeutic drugs, including carboplatin, etoposide, Adriamycin and vincristine, were used to treat the cell lines, in order to evaluate the sensitivity of RB cells. Furthermore, miR‑34a expression was detected by reverse transcription-quantitative polymerase chain reaction, and western blotting was implemented to quantify expression levels of MAGE‑A and p53. A luciferase reporter gene assay was used to validate the targeted association between miR‑34a and MAGE‑A. The results indicated that SO‑Rb50 cells exhibited the highest resistance to carboplatin, Adriamycin and vincristine (P<0.05), whereas HXO‑Rb44 cells revealed the highest inhibition rate in response to etoposide (P<0.05) out of the four cell lines. Furthermore, reduced miR‑34a expression and increased MAGE‑A expression significantly elevated the survival rate and viability of SO‑Rb50 cells following drug treatment (all P<0.05). miR‑34a was also demonstrated to directly target MAGE‑A, thereby significantly promoting the viability of RB cells and depressing apoptosis (P<0.05). p53, which was subjected to modulation by miR‑34a and MAGE‑A, also significantly reduced the proliferation rate of RB cells (P<0.05). In conclusion, the miR‑34a/MAGE‑A/p53 axis may be conducive to enhancing the efficacies of chemotherapeutic treatments for RB.