An efficient modified QuEChERS method combined with high performance liquid chromatography-tandem mass spectrometry detection (HPLC-MS/MS) was established and evaluated for the residue analysis of thifluzamide in rice grain, husk, straw, seedling, paddy water, and soil. Thifluzamide residues were extracted with acetonitrile, cleaned up with primary secondary amine (PSA), and then determined by HPLC-MS/MS. The fortified recoveries were 76%–106% with RSDs of 3%–13%. The results of the supervised field trials at two experiment sites showed that thifluzamide dissipated rapidly in paddy fields, and the half-lives in paddy water, soil, and rice seedling were 0.3–0.6 d, 1.8–3.6 d, and 4.3–13.9 d, respectively. At harvest time, when the preharvest interval (PHI) was set as 21 d, the final residues of thifluzamide in rice grains were below the maximum residue limit (MRL) of 0.5 mg/kg set by Japan, whereas the final residues in rice husk and straw were still high (the highest value reached 1.36 mg/kg in rice husk and 0.83 mg/kg in rice straw). The results indicated that the highest residue in rice grain was 0.23 mg/kg when PHI was 21 d, and only 6.9–11.0% of acute risk quotient of thifluzamide was occupied by the dietary daily intake in Chinese population consuming rice.