Mesoporous silica nanomaterials show great potential to deliver chemotherapeutics for cancer treatment. The key challenges in the development of injectable mesoporous silica formulations are colloidal instability, hemolysis and inefficient drug loading and release. In this study, we evaluated the effect of PEGylation of mesoporous silica nanorods (MSNR) on hemolysis, colloidal stability, mitoxantrone (MTX) loading, in vitro MTX release, and cellular MTX delivery under hypoxic conditions. We found that PEGylation prevented dose-dependent hemolysis in the concentrations studied (0-10 mg/ml) and improved colloidal stability of MSNR. A negative effect of PEGylation on MTX loading was observed but PEGylated MSNR (PMSNR) demonstrated increased MTX release compared to non-PEGylated particles. Under hypoxic conditions, a decrease in the IC50 of MTX and MTX-loaded MSNR was observed when compared to normoxic conditions. These results showed that MSNR could deliver the chemotherapeutic agent, MTX to tumor cells and induce effective cell killing. However, the effect of PEGylation needs to be carefully studied due to the observed adverse effect on drug loading.