Long-term exposure to ionizing radiation (IR) can cause dire health consequences even less than the dose limits. Previous biomonitoring studies have focused more on complete blood counts (CBCs), with non-coherent results. In this study, we aimed to investigate the association between exposure to IR and cytokine interleukin-6 (IL-6) along with hematological parameters in Tabriz megacity’s radiation workers. In this hospital-based study, blood samples were taken from 33 radiation workers (exposed group) and 34 non-radiation workers (control group) in 4 hospitals. Absorbed radiation dose was measured by a personal film badge dosimeter in radiation workers. The studied biomarkers and all of the selected covariates were measured and analyzed using adjusted multiple linear regression models. The exposed doses for all radiation workers were under the dose limits (overall mean = 1.18 mSv/year). However, there was a significant association between exposure to ionizing radiation and IL-6 (49.78 vs 36.17; t = 2.4; p = 0.02) and eosinophils (0.17 vs 0.14; t = 2.02; p = 0.049). The difference between the mean of the other biomarkers in radiation workers was not statistically significant compared to the control group. This study demonstrated that long-term exposure to ionizing radiation, even under the dose limits, is related to a significantly increased level of some blood biomarkers (Il-6 and eosinophil) that, in turn, can cause subsequent health effects such as cancer.