Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Here, we exploited the synergy between histone deacetylase inhibitors (HDACi) and cyclooxygenase 2 (COX-2) inhibitors by generating and testing a series of hybrid Celecoxib-HDAC inhibitors (selenium-containing analogues of Celecoxib) on ALL cells, of which compound 11 exhibited significant inducement to kill NALM6 cells with an average IC<sub>50</sub> of 9.95 ± 0.44 μM compared with control Celecoxib at 28.58 ± 1.44 μM and inhibited NALM6 cells growth via the inhibition of the cell cycle in G2 phase. Furthermore, compound 11 induced apoptosis by activating PARP cleavage. Taken together, compound 11 possessed the potential to be developed further as a chemotherapeutic agent for ALL.