Objective This study evaluated the effect of non-surgical periodontal therapy (NSPT) on the cytokine profile in gingival crevicular fluid (GCF) in patients with breast cancer and periodontitis. Methods Forty patients were allocated into the periodontitis group (P) (n = 20) and breast cancer with periodontitis group (BC/P) (n = 20). Two days before the removal of infectious foci from the oral cavity and NSPT, as well as periodontal reevaluations, C-reactive protein, neutrophils (10(3)mu L), and platelets (10(3)mu L), were evaluated. The following cytokines in GCF, interleukin (IL)-4, IL-10, IL-2, IL-6, IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and transforming growth factor-beta (TGF-beta) were evaluated by the Luminex assay at baseline, and 45 and 180 days after therapy. Cytokine levels were analyzed for correlations with the clinical parameters: clinical attachment level (CAL), probing depth (PD), bleeding on probing (BOP), and plaque index (PI). Results After NSPT, IL-2, TNF-alpha, and TGF-beta were downregulated (p<0.05) in the BC/P. In the P group, INF-gamma, IL-2, and TNF-alpha were downregulated (p<0.05), and TGF-beta was increased (p<0.05). At 180 days, IL-6 in GCF was significantly positively correlated with PD and CAL (r=0.45, r=0.56) in the BC/P (p<0.05). In the P group, IL-1 beta in GCF was positively correlated with PD and CAL (r=0.56, r=0.59) at 45 days (p<0.05). Conclusion NSPT, before the start of chemotherapy, helps to reduce the inflammatory markers associated with the activity of periodontal disease, favoring a less inflammatory pattern, to avoid the exacerbation of periodontitis.