Talaromycosis is a rare deep fungal infection caused by Talaromyces marneffei. Currently, methamphetamine has become the second-largest drug abuse category in the world after cannabis and has become a serious public health problem. Methamphetamine can inhibit human immune system and increase the probability of pathogenic microorganism infection. On 8 October 2016, a 20-year-old man with a fever history of 2 months was admitted to our hospital. He had bloody stools and abdominal pain during hospitalization. There was no significant abnormality in physical examination. Because of the misdiagnosis, he underwent improper treatment. Periodic acid-Schiff stain (PAS) staining showed that the mucosa of distal ileum, ascending colon, transverse colon, and sigmoid colon were infiltrated by a large number of tissue cells, which contained a large number of blue purple particles. In addition, a large number of histiocytes and multinucleated giant cells can be seen in the lamina propria of ileum mucosa, and fungal spores can be seen in histiocytes. Finally, he was diagnosed as talaromycosis and took itraconazole 0.2 g twice a day. After 5 days, the temperature dropped to normal and the inflammation disappeared, and he continued to take itraconazole for 6 months. Due to the neglect of the history of drug abuse and the concealment, drug-related talaromycosis is often misdiagnosed. Pathological examination is warranted for diagnosis talaromycosis. This condition requires a long-term anti-fungal therapy.