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Thrombocytopenia is commonly experienced with Temozolomide (TMZ) during treatment for Glioblastoma (GBM). With the increasing prevalence of obesity and associated Non-Alcoholic Steatohepatitis (NASH) worldwide, chronic thrombocytopenia is becoming increasingly common, and necessitates modifications in the standard of care treatment regimen for GBM. To date, no guidelines are present addressing this dilemma. We present a case of a patient with newly diagnosed GBM and NASH-associated cirrhosis with chronic thrombocytopenia and baseline platelet count of approximately 70,000/ μL. She received brain radiation alone followed by 6 cycles of adjuvant TMZ, initially with a 50% dose reduction and subsequent dose increase based on tolerability and stability of platelet counts. This case demonstrates the relative safety of TMZ in a patient whose platelets are affected by liver disease as opposed to bone marrow insufficiency.