Proton pump inhibitors (PPIs) are generally safe, and their short-term use commonly does not induce hemolytic anemia. The underlying mechanisms are unknown, and the literature insufficiently explores hemolytic anemia as an adverse event induced by PPIs. In this case study, we report a 31-year-old female who had developed hemolytic anemia with symptoms of jaundice, hyperbilirubinemia, and high reticulocytes, after treatment with PPI. Interestingly, the patient completely recovered after PPI withdrawal. This present case study highlights the need for physicians to exercise caution when treating patients with PPI.