A 61-year-old woman underwent an open right hemicolectomy for perforated ascending colon cancer. Later, the patient underwent R2 surgery for duodenal invasion. Chemotherapy was initiated with mFOLFOX6 and panitumumab post-surgery. Subsequently, oral minocycline was administered for the acne-like rash caused by panitumumab 19 days after the first treatment course. The patient showed a significant decrease in platelet count to 2.3×104/μL 18 days after oral medication initiation. However, platelet count improved to 10.6×104/wL 1 week after stopping minocycline. The timing of the decrease in platelet and white blood cell counts indicated minocycline as the suspected cause of thrombocytopenia, possibly during its administration to treat the acne-like rash, which was caused due to the anti-EGFR inhibitor side effects. Overall, this study highlights the need to monitor and manage minocycline-induced thrombocytopenia during chemotherapy.