Background Chronic pain is still lack of effective and safe treatment at present, so its mechanism has been more emphasized. Studies have found that P2X4 receptors play an important role in pain signal transduction in the recent years. Objective To illuminate the role and mechanism of P2X4 receptor in chronic pain. Content The review summarized the effect and mechanism of P2X4 receptors in chronic pain such as neuropathic pain﹑inflammatory pain and cancer pain. Trend We will provide a new idea for the treatment of chronic pain.