Endosulfan is a persistent pesticide that has been in use for more than five decades. During this time, it has contaminated soil, air, and water reservoirs worldwide. It is extremely toxic and harmful to beneficial non-target invertebrates, aquatic life, and even humans upon consumption, which is one of the many dangers of this pesticide since it biomagnifies in the food chain. The effects of three endosulfan concentrations (1, 10, and 100 µg/L) on the freshwater snail Physella acuta, an invasive cosmopolitan species, were examined over a week-long exposure period. Alterations in the expression of ten genes related to stress and xenobiotic detoxification were measured against the endogenous controls rpL10 and GAPDH by Real-Time polymerase chain reaction. Four genes are described here for the first time in this species, namely Hsp60, Grp78, GSTk1, and GSTm1. The rest of genes were Hsp90, sHsp16.6, cyp2u1, cyp3a7, cyp4f22, and MRP1. cyp2u1, sHsp16.6, and Grp78 expression were all altered by endosulfan. These results suggest a low pesticide concentration activates the acute response in P. acuta by affecting detoxification and stress responses and alter endoplasmic reticulum function and lipid metabolism. Furthermore, the newly identified genes extend the number of processes and cellular locations that can be analyzed in this organism. Endosulfan, also known as Thiodan or Thionex, is a polychlorinated compound used as a pesticide or acaricide. It has been in use since the 1950s in China, the European Union, Australia, Mexico, the United States, and India 1 for crops including maize, soybeans, tomatoes, and cotton 2. It is particularly effective in removing aphids, fruit worms, beetles, leafhoppers, moth larvae, and whiteflies 3. However, its highly toxic properties can potentially harm humans and wildlife 4,5. Further, due to its semi-volatility, endosulfan is often found thousands of kilometers away from its intended area of action in soil, water reservoirs, sediments, and even Arctic and Antarctic lakes. These findings prove its persistent character; indeed, it is listed as a persistent organic pollutant in the atmosphere, soil, and water by the Stockholm Convention 6. For this reason, it has been banned in over 80 nations. However, one of the main problems with pesticides as endosulfan is the fact that they are persistent and can be dispersed from air to water bodies. The environmental presence of endosulfan has been evaluated by Mohamed et al., 2019 7 showing values from 0.036 μg/L to 62.3 μg/L in water bodies. Indeed, it is an extremely toxic and harmful compound to beneficial non-target invertebrates living in aquatic media 8-10. Endosulfan is commercially available as a mixture of its isomers, α and β, but higher environmental concentrations correspond to α-endosulfan, since β-endosulfan is naturally converted into α-endosulfan in a slow way due to its higher stability 3. Although they share similar chemical and physical properties, under aerobic conditions the β-endosulfan half-life is approximately 28 days, ...