Herein, using 2D and 3D in vitro models, we showed that the pan-HDAC inhibitor Givinostat embedded in liposomes counteracts GBM cell growth by inducing: (1) a dose- and time-dependent reduction in cell viability; (2) a reduction in LDLR, LRP1, and VLDLR protein receptors; (3) a mild reduction in ABCA1 levels; and (4) an increase in cleaved Caspase-3. This evidence concerns the gene VLDLR and glioblastoma.