Background: At work, farmers are more likely to come into contact with pesticides and other agricultural contaminants. The permanent inhibition of acetylcholinesterase (AChE) at nerve synapses is thought to be a systemic impact of organophosphates (OPs). However, several investigations have shown that AChE inhibition alone does not account for all toxicological effects associated with longterm OP exposure. Although oxidative stress and epigenetic modifications are two of the most recently hypothesized mechanisms, the existence of genetic variations appears to have the greatest influence on biological outcomes. Objectives: The purpose of this study is to investigate the polymorphisms in genes that code for OPs metabolizing enzymes. Because the glutathione-S-transferase (GSTM1) and paraoxonase (PON1) genes encode enzymes that breakdown pesticides with carcinogenic potential, we're particularly interested in them. Methodology: From June to December 2018, a cross-sectional study was done on 24 pesticide applicators and 25 corresponding controls. Serum AChE activities were determined using the EQM Test-Mate kit. Using polymerase chain reaction-restriction fragment length polymorphism, the influence of genetic polymorphism in GSTM1 and PON1 on OPs exposure was examined. Results: Compared to the control group, chronically exposed patients had significantly lower serum AChE enzyme activity (<0.001). In terms of the GSTM1 polymorphism and the R allele of the PON1 (Q192R) polymorphism, there was a significant difference between chronic OP exposed cases and controls. The PON1 (LM) polymorphism was found to be of little consequence. Conclusion: Finally, the GSTM1 and R allele of PON1(LM) polymorphisms may be a risk factor for chronic organophosphates intoxication in Egyptian pesticide applicators.