For the first time, an analysis of structural damage of the peripheral blood erythrocyte nucleus in Rutilus rutilus (Linnaeus, 1758) was carried out for the rivers of the north-western region of Ukraine. The effect of the hydrochemical regime on the formation of cytogenetic disturbances of the representatives of this species was also clarified. It was observed that during 2013–2017, the content of phosphates, suspended solids, fluorides, iron, copper, zinc, manganese, nitrite nitrogen and nitrate nitrogen in the surface waters of rivers most significantly exceeded the current quality standards. The average frequency of nuclear disorders of peripheral blood erythrocytes R. rutilus from the studied hydrosystems is 5.25 ± 0.29 ‰ (p < 0.01), with a noticeable excess of the level of spontaneous mutations in the older age groups of fish. In all analyzed samples of R. rutilus, among the total number of identified structural disorders of the nucleus, the largest share is made up of red blood cells from the micronucleus (from 40.0 to 62.0 %), which is evidence of cytogenetic disturbances in the body of fish. At the same time, disturbances of erythrocyte blood of roach from small rivers are on average 1.3 times (or 21.9 %) higher compared with individuals from medium-sized rivers. The formation of cytogenetic disturbances in R. rutilus under the conditions of the hydrochemical regime of rivers is described by a close (r = 0.99 at p < 0.003) multifactorial regression dependence. More important regressive coefficients of the dependency are acquired by such biogenes (NH4+, NO3−, PO4−) and toxicants (Cu2+, Zu2+, Mn2+, F2) in the background of oxygen regime peculiarities (COD, BOD5, O2).