Background: Acute pulmonary embolism (PE) as the first sign of hepatocellular carcinoma (HCC) is rare. It is a deadly disease with high morbidity and mortality. Despite the high prevalence of PE, the diagnosis is still challenging, mainly due to the unpredictability of symptoms. The stratification of acute pulmonary embolism is important because it determines the right steps in decision-making. Case Illustration: A 45-year-old man went to a private hospital's emergency room (ER) with sudden shortness of breath. He was desaturated and shocked. He was assessed as having an acute coronary syndrome (ACS), got loaded with dual antiplatelets, and was referred to our hospital. We rule out ACS because the patient's complaint is sudden shortness of breath and desaturation. Acute PE was diagnosed after bedside transthoracal echocardiography (TTE) in the ER revealed right ventricular (RV) dysfunction. We continued with the computed tomography pulmonary artery (CTPA) examination and found a thrombus in the pulmonary artery. We assessed patients with high-risk PE and performed thrombolysis. Initially, we suspected unprovoked PE because we did not find a clear trigger, such as malignancy, prolonged bedriddenness, recent surgery, or old age. We accidentally found HCC from the patient's CTPA evaluation, and HBsAg was reactive. Conclusion: Every case of dyspnea that shows up at an emergency room should have acute PE taken into consideration in the differential diagnosis. In patients with suspected PE without obvious risk factors, we can use CT to triple-rule out ACS, aortic dissection, and pulmonary embolism. Patients treated with thrombolytic therapy show rapid improvement, which may lead to a lower rate of mortality and morbidity. Keyword: Acute Coronary Syndrome, Acute Pulmonary Embolism, Hepatocellular Carcinoma, Thrombolysis, Unprovoked.