In the present work, we report a facile and simple strategy to functionalize graphene with the chloromethyl (CHCl) functional group as a nanoplatform for effectual loading of the 5-fluorouracil (5-FU) anticancer drug. To achieve the highest loading capacity, hydrochloric acid concentration, the quantity of paraformaldehyde, ultrasonic treatment time, and stirring duration were all carefully optimized. The results revealed that the optimum conditions for functionalizing graphene were obtained at 70 mL of hydrochloric acid, 700 mg of paraformaldehyde, and times of 35 min and 2 h of ultrasonication and stirring. Later, the drug (5-FU) was loaded onto CHCl-functionalized graphene through hydrogen bonding and π-π interactions. The chemical structure of the functionalized material and the loading of the 5-FU drug were confirmed by FTIR analysis, scanning electron microscopy, and X-ray photoelectron spectroscopy. The 5-FU loading capacity of as-prepared materials was determined using the ion chromatography instrument. Our findings demonstrate that chloromethylated graphene is a very excellent nano-platform for high-efficiency drug loading, yielding a loading capacity of 52.3%, comparatively higher than pure graphene (36.54%).