Objective We aimed to evaluate the enzyme activity of chitotriosidase as a biomarker in early diagnosis silicosis and to investigate immune system response and oxidative stress caused by silica exposure. Materials and Methods Silicosis patients (n = 116), exposed to silica without disease (n = 76), and healthy individuals (n = 55) were included. Serum levels of chitotriosidase, proinflammatory cytokines, oxidant-antioxidant, and immune parameters were measured. Results Serum chitotriosidase enzyme levels in the silicosis group were statistically significantly higher than the exposure and control groups. Inflammatory biomarkers and 8-hydroxy-2-deoxyguanosine levels were found to be statistically significantly higher in the silicosis and exposure group compared with the controls, while superoxide dismutase and glutathione peroxidase were lower. Conclusions Increased serum chitotriosidase level emerged as a biomarker that can not only distinguish silicosis from exposure and healthy controls but also indicate early pulmonary effects of silica.