Paraquat poisoning usually results from suicide, occupational, or accidental exposure. Herein, we report a rare fatal case of homicidal paraquat poisoning. A 58-year-old man was poisoned by taking paraquat-mixed medicine and wearing paraquat-soaked underwear. In the absence of a history of paraquat exposure, the patient was misdiagnosed with pulmonary infection and scrotal dermatitis and died of respiratory failure 24 days after the initial exposure to paraquat. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to detect and quantify paraquat in postmortem specimens. The concentration of paraquat in postmortem specimens from high to low is lung (0.49 μg/g), brain (0.32 μg/g), kidney (0.24 μg/g), liver (0.20 μg/g), cardiac blood (0.11 μg/mL), and stomach wall (<LOQ). Identification of homicidal paraquat poisoning is not easy for a clinician or a forensic pathologist, it is important to consider the possibility of paraquat poisoning when patients suffer from rapidly aggravating pneumonia of unknown origin.