Objective: This study aims to assess the impact of prolonged occupational exposure to chrysotile asbestos on the epithelial cells of the upper respiratory tract and the levels of surfactant protein D (SP-D) in female workers. Methods: Buccal epithelial cell samples were collected from 40 workers at JSC “Kostanay Minerals”, fixed using the May–Grünwald method, and stained with the Romanowsky–Giemsa technique. SP-D levels were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Workers exposed to asbestos dust exhibited a significant increase in cytological abnormalities and higher SP-D levels compared to the control group. Conclusion: Prolonged exposure to chrysotile-containing dust leads to degenerative changes in upper respiratory tract epithelial cells, characterized by cytological and cytogenetic abnormalities, alongside elevated SP-D levels, highlighting the need for preventive health measures.