Most ophthalmic surgeries are characterized by small incisions and mild pain, therein, the choice of topical anesthesia can meet the needs of surgeries and accelerate ophthalmic surgeries to be conducted in day surgery model. 0.4% oxybuprocaine hydrochloride eye drops is one of commonly used topical anesthetics for ophthalmic surgery, which has the characteristics of rapid onset and sufficient analgesia with long duration (about 13 minutes). Oxybuprocaine hydrochloride eye drops has been widely and safely used in intraocular surgery without affecting the pupil and blood vessels. Meanwhile, oxybuprocaine hydrochloride eye drops has negligible effects on corneal thickness and corneal epithelial thickness to meet the needs of refractive surgery. In addition, oxybuprocaine hydrochloride eye drops can provide sufficient postoperative analgesia, reduce the use of postoperative analgesics and the incidence of emergence agitation in children after strabismus surgery. The preservative-free topical anesthetic would be one of ideal topical anesthetics as it can provide a good surgical condition and reduce complications and risks of post-operative infections without changing the onset time and analgesia effects. This article provides a review of the mechanism, analgesia, pharmacokinetics, clinical efficacy, and safety profiles of 0.4% oxybuprocaine hydrochloride eye drops.