Background <p>L-Asparaginase is a medically important enzyme known to be a chemotherapeutic agent and is often used in multi-agent chemotherapeutic regimens. L-Asparaginase can inhibit the growth of malignant cells by rapidly eliminating two vital amino acids, L-glutamine and L-asparagine.</p> Main text <p>Despite many benefits shown by L-Asparaginase in the therapy of lymphocytic leukemia, its application is accompanied by serious side effects, e.g., leucopenia, immunosuppression, acute pancreatitis, thromboembolism, hyperglycemia, neurological seizures, plasminogen, protein C and protein S, and antithrombin III. Recently, nanotechnology has entered medical sciences to increase the efficiency of therapy and decrease the associated side effects of cytotoxic anti-cancer agents. Immobilization of L-asparaginase on solid supports, in particular on the surface of nanocarriers, represents an effective way of increasing operational stability and reusability while decreasing side effects by mediating selective accumulation of the enzyme in cancerous tissues.</p> Conclusion <p>This article focused on the application of nanocarriers for improving the therapeutic benefits of L-asparaginase, which may open new horizons for pharmaceutical industries to provide new anti-cancer nanomedicines based on L-asparaginase.</p>