Background: Sertraline (ST) hydrochloride is an anti-depressant of the selective serotonin reuptake inhibitor (SSRI) class. Potentiometric sensors are an appealing route for detecting drugs due to some advantages in terms of sensitivity, feasibility, selectivity, fast response, tolerance to turbidity and colour of solutions, and cost-effectiveness. Methods: A mixture of polyvinyl chloride powder (PVC) with o-nitrophenyl octyl ether and the ion asso- ciation complex was dissolved in tetrahydrofuran (THF) to prepare the membrane for the proposed sen- sor. The sensor was calibrated and then electrochemically used for detecting ST in pharmaceutical sam- ples. Results: The near Nernstian response was observed for a concentration of 1.0 x 10-8 - 1.0 x 10-2 mol L-1 with 58.62 mV as a slope per concentration decade. This direct potentiometric measurement resulted in average recoveries of 96.0 ± 0.2%. Moreover, good selectivity for sertraline with respect to many inor- ganic and organic cations was observed. Conclusion: The proposed sensor was simple to use and produced accurate and precise results. The mole- cule's chemical and biological activities were revealed using theoretical calculations. Regarding the chem- ical activities, calculations were made on the 3-21g and 6-31g while the SDD bases were set at B3LYP, HF, and the M062X level. Molecular docking calculations were designed against cancer proteins in order to have details regarding the molecule's biological activity