Rationale: Osteopetrosis is a rare disease that predominantly occurs in descendants of inbreeding families. In the case of fractures happen in patients with osteopetrosis, the choice between operative or conservative treatment is still controversial. Open reduction and internal fixation (ORIF) is a conventional treatment for fractures, and it possesses more applicability than conservative treatment. During this surgical treatment, ensure that bone union in the right way is pivotal to success and simultaneously prevents refracture and displacement after the operation. Herein, we present a case of femoral fracture of a patient with osteopetrosis via open reduction and internal fixation. To illustrate successful factors during the treatment process, we discuss experience combined with literature review following case report. Patient concerns: A 67-year-old man who has diagnosed with osteopetrosis over 20 years ago suffered from pain in the left hip last for more than 1 month and he was incapable of walking recently. Before this incident, he had sustained 4 femoral fractures that treated insufficiently by open reduction surgery. Diagnosis: Physical, radiological, and biological examinations indicated a femoral subtrochanteric fracture that was overlapping displacement between fracture ends. Interventions and outcomes: Treated with surgery by open reduction with internal fixation and osteotomy, the fracture united in 12 months, and he returned to walk with full weight bearing, during which no complication occurred. Lessons: Open reduction and internal fixation is also suitable for the patient with osteopetrosis, and they have similar union ability to the normal. To guarantee successful treatment, specific strategies of operation and rehabilitation program are necessary.