Keratoconus (KC) is a degenerative corneal disorder whose aetiology remains unknown. The aim of our study was to analyse the expressions of cytokines and chemokines in KC patients before and after specified time intervals after corneal cross-linking (CXL) treatment to better understand the molecular mechanisms occurring before and after CXL in KC patients process of corneal regeneration.; Tear samples were gathered from 52 participants immediately after the CXL procedure and during the 12-month follow-up period. All patients underwent a detailed ophthalmological examination and tear samples were collected before and after CXL at regular intervals: 1 day before and after the surgery, at the day 7 visit, and at 1, 3, 6, 9, and 12 months after CXL. The control group consisted of 20 healthy people. 10 patients were women (50%) and 10 were men (50%). The mean age was 30 ± 3 years of age. Tear analysis was performed using the Bio-Plex 3D Suspension Array System. Corneal topography parameters measured by Scheimpflug Camera included: keratometry values (Ks, Kf), PI-Apex, PI-Thinnest, Cylinder.; All the 12 months post-op values of the KC patients' topographic measurements were significantly lower than the pre-op. As for the tear cytokine levels comparison between the patient and control groups, cytokine levels of TNF-α, IL-6, and CXCL-10, among others, were detected in lower amounts in the KC group. The pre-op level of IL-6 exhibited a significant increase the day after CXL, whereas comparing the day after the procedure to 12 months after CXL, this showed a significant decrease. Both TNF-α and IL-1 showed a significant decrease compared to the day before and after CXL. We observed significantly higher levels of IL-1β, IL-10, IFN-γ and TNF-α in moderate and severe keratoconus than in mild keratoconus (p < 0.05). We also demonstrated a statistically significant positive correlation between both pre-op and 12 months after CXL TNF-α, IFN-γ, IL-6 and Ks and Kf values (p < 0.05, r > 0); Alterations of inflammatory mediators in tear fluid after CXL link with topographic changes and may contribute to the development and progression of KC.