The invention provides a tegafur derivative containing a 1,3,4-thiadiazole heterocyclic ring and an amide group. The structural formula of the tegafur derivative is as shown in the specification. A preparation method of the tegafur derivative comprises the steps of (1) dissolving a 3-(methoxycarbonylmethyl)tegafur in methanol, dropwise adding a sodium hydroxide solution, extracting by using ethyl acetate and distilled water and separating out an organic layer and a water layer, next, extracting by using ethyl acetate and blending the organic layers, and adding anhydrous sodium sulfate to obtain 1-(tetrahydro-2-furyl)-3-carbethoxy-5-fluoro-2,4-pyrimidinedione; (2) blending 1-(tetrahydro-2-furyl)-3-carbethoxy-5-fluoro-2,4-pyrimidinedione with dioxane, then adding sulfoxide chloride to obtain a 1-(tetrahydro-2-furyl)-3-chloracetyl-5-fluoro-2,4-pyrimidinedione solution, and then adding dioxane, evenly mixing and then sealing for later use; (3) taking 2-amino-5-p-nitrophenyl-1,3,4-thiadiazole, dioxane and triethylamine, and dropwise adding the 1-(tetrahydro-2-furyl)-3-chloracetyl-5-fluoro-2,4-pyrimidinedione solution obtained in the step (2) to obtain a pure product 1-(tetrahydro-2-furyl)-3-acetamido-[5-p-nitrophenyl-(1,3,4-thiadiazole-2-yl)]-5-fluoro-2,4-pyrimidinedione. The tegafur derivative has anti-tumor effect and no obvious toxicity, and is used for clinically treating malignant tumors.