This study was to evaluate the desensitizing efficacy of polymeric nano calcium fluoride containing varnish compared with Casein phosphopeptide amorphous calcium phosphate containing fluoride varnish in reducing Dentin hypersensitivity. Methodology: in a randomized control trial, (100 lesions) in patients with chief complaint of generalized dentin hypersensitivity of the outpatient clinic in the restorative department, Faculty of dentistry, Cairo University; were enrolled then randomly allocated into one of the two groups according to the desensitizing agent was used either polymeric nano calcium fluoride varnish (OliNano SEAL®) or Casein phosphopeptide amorphous calcium phosphate fluoride varnish (MI varnish®). Sensitivity was confirmed by tactile and air test, each participant should have sensitive lesions with a visual analogue scale (score two or more). The manufacturer’s instructions were followed during the varnish application. Degree of dentin hypersensitivity was assessed by VAS scale in response to Air test, while Schiff score was used in response to air water test. Records were collected at baseline T0, immediately after varnish application T1, 3 months T2 and 6 months later T3. Patients were instructed to follow the post – treatment protocol. The significance level was set at P ≤ 0.05. Statistical analysis was performed with IBM® SPSS® Statistics Version 20 for Windows.