Inappropriate management of industrial effluents has been among major causes of water pollution and subsequent fish physiological and behavioral disorders and mortalities. This study investigated the effects of wastewater from a paper mill on immune-related gene expressions (lysozyme, tumor necrosis factor and heat shock protein 70) and hematological alterations, in juvenile rainbow trout (Oncorhynchus mykiss) during a 14-day exposure period. Following the determination of LC50, fish (135 +/- 10 g body weight) were exposed to three effluent treatments: control (0), 10 and 25% of LC50, in laboratory conditions. The wastewater exposure initially increased lysozyme and tumor necrosis factor gene expression, and the expression of both genes was suppressed on the 14th day after exposure. There was a rise in heat shock protein 70 gene expression at the beginning of the experiment and then decreased to the level observed in the control group. Fish exposed to wastewater showed a significant increase in the levels of red blood cells, white blood cells and hematocrit three days following exposure, but the levels of these blood parameters significantly decreased at the end of the exposure period (P < 0.05). Our results indicated a range of immune-related gene toxicity and hematotoxicity in rainbow trout caused by the negative impacts of the industrial wastewater. Here we also discussed that poor biosecurity controls and inadequate treatments of effluents from industrial activities can lead to serious damages among wild populations.