The present study, pointed to assess heavy metal accumulation like Aluminum (Al), Cadmium (Cd), Chrome (Cr), Cobalt(Co), Copper(Cu), Iron(Fe), Lead (Pb), Manganese(Mn), Nickel(Ni), Selenium(Se) and Zinc(Zn) in water, sediments and liver of Oreochromis niloticus, which collected from sewage water in El-kharja, New Valley, Egypt using inductively coupled plasma mass spectrometry (ICP-MS). Also, the histopathological changes of liver of Oreochromis niloticus were reported. These histopathological changes were detected using different staining types as a pollution biomarker. Iron showed the highest accumulation level in water (9.06±0.86 ppm), sediments (175.1±20.8 ppm) and liver (158.17±38.59 ppm), followed by Al> Mn> Ni> Zn> Pb> Cr> Se> Cu> Co> Cd. However, these elements showed Fe> Al> Ni> Mn> Cr> Cu> Zn> Pb> Cd> Se> Co accumulation trend in sediments. In liver these metals showed Fe> Se>Al> Zn>Mn> Cu>Ni> Cr> Pb> Co> Cd trend. Histopathological examination of fish liver showed signs of progressive alterations such as disorganization of architecture of liver cells, hydropic degeneration and vacuolation of hepatocytes. Also, dilation and congestion in blood sinusoids, hypertrophic and increase in number of küpffer cells were chronicled. Sever deposition of hemosiderin pigments were reported while necrosis with pyknotic nucleus and focal histopathological characters were observed side by side with normal cell. Our results concluded that water, sediment and liver accumulation toxicity tests and histopathological changes of liver may be associated, and these approaches may be used together to describe the environmental state and water quality assessment.