Thrombocytopenia can cause substantial morbidity and mortality in critically ill patients. There are multiple etiology factors and various mechanisms associated with thrombocytopenia, of which drug-induced thrombocytopenia (DITP) deserves attention. Herein, we describe a case of severe thrombocytopenia during intensive care unit (ICU) hospitalization that was probable to be associated with vancomycin. In addition, clinical studies evaluating thrombocytopenia caused by vancomycin were systematically reviewed and 6 studies with acceptable quality were included and analyzed. By revealing the process of identifying this case of DITP and reviewing relevant clinical studies, a risk alert of vancomycin related severe hematotoxicity should be focused on.