A plasma gun for treating a tumor in vivo and a use method thereof. The plasma gun includes a generator component including an ionization device and a shield element, and a discharge component. The ionization device is provided at the shield element, and the discharge component is connected to an end of the shield element. The present invention overcomes the problem that a low-temperature plasma jet cannot contact a tumor in vivo. The plasma gun reaches the interior of the tumor, promoting the treatment of the plasma to the tumors. It is suitable for the application in clinical treatment. As compared with the conventional radiotherapy, chemotherapy and surgery, the present invention has the advantages of selectivity on cancer cells and little side effects. The plasma directly reaches the tumor lesion, which has good therapeutic effect and avoids the impact on normal tissues.