Introduction: Propofol is used in injectable form intravenously by anesthetists for the induction of anesthesia. It is the drug of choice in short or daycare surgical cases. The patients who experience pain, are also able to experience anxiety and fear. In the most severe cases, they can also face myocardial infarction and ischemia. Aim: A comparison of pain-alleviating effects of Lignocaine, Dexamethasone, Pethidine, and placebo in a patient caused by the administration of Propofol for the induction of anesthesia. Methodology: The study included 144 patients who had been given an injection of Propofol for the induction of anesthesia. The patients were divided into four groups as four types of drugs were administered. The allocation of the participants was done randomly. The age range of the patients was from 18-62 years. All the participants were undergoing upper abdominal surgery. After the administration of 25% Propofol, the patients were asked for their status of pain. A randomized controlled trial. This study was conducted at Chandka Medical College, SMBBMU Larkana, Pakistan from April 2020 to April 2021. Results: The drugs Lignocaine, Dexamethasone, and Pethidine reduced the pain caused by injection of Propofol as compared to the placebo. The pain score in these three drug groups was not significantly different. Also, the recall of pain in these groups was not significantly different. However, the difference between the placebo group and the remaining three groups was significant. Conclusion: Lignocaine, Dexamethasone, and Pethidine significantly reduce the pain caused by the Propofol injection as compared to a placebo. There is no significant difference between their efficacies. Nonetheless, the difference between the previously mentioned drugs and placebo is significant.