The cytochrome P450 superfamily (cyp < /em>) is a unique, diverse group of enzymes that catalyze the oxidation of organic pollutants such as polycyclic hydrocarbons (PAHs). Both levels of cyp1a expression in Oreochromis aureus organs and the accumulation of PAHs in water were determined in five different locations of Lake Manzala; namely, El-Inaniya, El-Serw, El-Temsah, El-Gamil, and El-Bashtir during December 2011. The area of Al-Qanater was included as a reference site from the River Nile. The cyp1a gene was highly expressed in the liver of all fish populations followed by gill, testis, ovary and muscle. The liver and gonads of the fish population in the El-Gamil location exhibited the greatest cyp1a gene expression, while the gills and muscles in the El-Serw fish population were the highest in the expression pattern among Lake Manzala regions. A higher accumulation profile of PAHs in water was found in the El-Gamil location followed by El-Serw, El-Bashtir, El-Inaniya and El-Temsah. The correlation between PAHs and cyp1a expression of fish organs showed a significant positive correlation. The highest positive correlation was observed between the gill and liver based on the expression of cyp1a. The obtained cDNA of the cyp1a gene from O. aureus was 569 base pairs, and it exhibited 86.8% of the identity with cyp1a of O. niloticus. The phylogenetic tree of cyp1 family genes showed a closer relationship between cyp1a and cyp1d subfamily compared to cyp1b or cyp1c subfamily members. The results showed the sensitivity of cyp1a expression in fish as a biomarker for PAHs concentrations in the regions of Lake Manzala.