The effect of HA on the serum level of pro-inflammatory cytokines and host response to inflammation biomarkers had not been previously investigated; therefore, the objective of this study was to evaluate the effect of subgingival administration of 0.8% hyaluronic acid gel (GENGIGEL®) as an adjunct to surface root debridement on clinical periodontal parameters, pro-inflammatory cytokines (IL-1 beta and TNF-alpha), and biochemical disease markers (CRP and ALP) in a group of patients with periodontitis in comparison with CHX and SRD groups. Here, TNF is linked to periodontitis.