'painkiller' originates from English, formed as a compound of the noun 'pain' and the agent noun 'killer' in the mid-19th century. 'Pain' ultimately comes from Old French 'paine' and Latin 'poena' meaning 'punishment' or 'suffering', while 'kill' derives from Old English roots (e.g. 'cwellan') meaning 'to put to death', with the agentive suffix '-er' producing 'killer'.

'pain' changed from Latin 'poena' → Old French 'paine' → Middle English 'pein'/'payn' → modern English 'pain'. 'Kill' comes from Old English (e.g. 'cwellan') → Middle English (e.g. 'killen') → 'kill'. The compound 'pain-killer' was formed in English in the 19th century and became the modern 'painkiller'.

Initially it was a literal compound meaning 'something that kills pain'; over time this stabilized into the medical/common sense 'a substance or drug that relieves pain'.