Immune and antioxidant-related genes reflect the immune response of fish against different ecosystem circumstances around it. The present study is concerned with the effect of industrial and sewage effluents in some water drainages on immune and antioxidant-related genes of the Nile tilapia (Oreochromisniloticus). Fish specimens were collected from three different places; the first group was collected from El-Rayah El-Towfeky stream, Tokh, which receives loads of sewage and agricultural effluents (site A). The second group was collected from El-Sharkawia stream, Shoubra El-Khama, which receives industrial wastes (site B). The third group (site C) was collected from a fish farm in Al-Fayoum City (supplied with clean water) and was considered the control group. The expression of some immune-related genes (inf1α, csf1r, igmh, and il1b) and antioxidant genes (sod, cat, and gr) was determined in the liver and head kidney of the fish. The results revealed that the highest expression of most immune-related genes in the liver and kidney of the Nile tilapia was recorded in fish collected from site B. Regarding antioxidant genes, the highest catalase (cat) expression was recorded in the liver and kidney of the Nile tilapia maintained in sites A and B, respectively. Again fish from site B showed the highest superoxide dismutase (sod) and glutathione reductase (gr) expression in the kidney compared to the fish from other sites (although the differences were not statistically significant). The only highest expression found in fish in site C was reported in superoxide dismutase (sod) and glutathione reductase (gr) expression in the liver.  Interestingly, the results revealed the positive influence of industrial pollution in some drainages on the Nile tilapia's health.