Patients with nephrotic syndrome carry a high risk of pulmonary embolism due to the abnormalities in coagulation and fibrinolysis. Thrombolytic therapy for critical pulmonary embolism in nephrotic syndrome patients was rarely reported and remains controversial in the regimen selection so far. We reported a case of fatal pulmonary embolism, complicating in hepatitis B virus-associated nephrotic syndrome. The patient presented with chest pain, hemoptysis and shortness of breath on admission and his initial vital signs showed a high risk of developing hypotension. Urgent radiological examinations confirmed massive embolisms in bilateral pulmonary arteries. Prompt thrombolytic therapy was performed right after the diagnosis of pulmonary embolism with an intravenous infusion of urokinase (20 000 U/kg) in 2 h. Complete resolution of pulmonary embolism was achieved after urokinase administration and the patient was discharged in good conditions. This report highlighted the efficacy and safety of prompt thrombolytic therapy with urokinase for nephrotic syndrome patients presented with massive pulmonary embolism. In this study, we also briefly discuss the recent findings on the current state of urokinase in the clinical practice of thrombolysis.