Chemotherapy-induced thrombocytopenia (CIT) is a common condition that frequently results in reduced chemotherapy dosages, postponed treatment, bleeding, and unfavorable oncological outcomes. At present, there is no clear suggestions for preventing or treating CIT. Thrombopoietin (TPO) replacement therapy has been invented and used to treat CIT to promote the production of megakaryocytes and stimulate the formation of platelets. However, this treatment is limited to the risk of immunogenicity and cancer progression. Therefore, an unmet need exists for exploring alternatives to TPO to address the clinical issue of CIT. Application of appropriate therapeutic drugs may be due to understanding the potential mechanisms of CIT. Studies have shown that chemotherapy significantly affects various cells in bone marrow (BM) microenvironment, reduces their ability to support normal hematopoiesis, and may lead to BM damage, including CIT in cancer patients. This review focuses on the epidemiology and treatment of cancer patients with CIT. We also introduce some recent progress to understand the cellular and molecular mechanisms of chemotherapy inhibiting normal hematopoiesis and causing thrombocytopenia.