Pseudomonas aeruginosa can regulate different group actives and physiological processes through the quorum sensing mechanism. The aims of this research were to detect the presence of quorum sensing genes in 50 clinical P. aeruginosa isolates, which represent by (lasI, lasR, rhlI, and rhlR) and Pseudomonas quinolone signal (PQS) (PgsA, PgsB, PgsC, PgsD, PgsE, and MvfR) genes by Polymerase chain reaction (PCR) technique and interaction between the two systems. Isolates were subjected to test their susceptibility to 12 antimicrobial drugs, 64% of isolates showed resistance to ceftazidime, followed by carbencillin (56%), while only 8% were resistant to imipenem. In addition, all of the bacterial isolates were distributed within three multidrug-resistant (MDR) patterns, viz., A, B, and C. The highest rate of MDR was showed with MDR pattern C, in which bacterial isolates showed resistance to resist (9→11) antimicrobial drugs. Results revealed that P. aeruginosa isolates have different gene patterns, viz., A to E. According to quorum sensing genes production, pattern A found to express all the genes in LasI, RhI, and PQS system, while pattern B has a defective for the production of lasR, rhlR genes, while the same isolates have the PQS system all present. Significantly, there is a positive relationship between las and rhl system and regulation of antibiotics resistance, in which the bacterial isolates that have las and rhl genes showed high resistance to common antimicrobial agents under study. These findings suggest that PQS can function as an intercellular signal in P. aeruginosa that is not restricted only to alkyl homoserine lactones (AHL).