Background Alopecia areata (AA) is a common immune-mediated disorder. Destruction of anagen hair follicles by cytotoxic T cells (CTL) plays a major role in the pathogenesis of AA. Serum granulysin has been shown to reflect overall activity of CTLs. Aims In this study, we aimed to compare serum granulysin levels in patients with AA before and after therapy and to analyze correlation between serum granulysin levels and disease severity. Methods We evaluated the Severity of Alopecia Tool (SALT) score and serum granuysin levels of 38 AA patients at baseline and at 6th month of therapy. Thirty-three patients were treated with tofacitinib 5 mg b.i.d, and five patients were treated with topical immunotherapy. Serum granulysin levels were measured by enzyme-linked immunosorbent assay. Results A moderate correlation was found between SALT scores and serum granulysin level at baseline (r = .378,P = .019). Baseline serum granulysin levels were significantly higher in patients with alopecia totalis/universalis compared with patients with patchy AA (P = .004, Z = 2.778). Serum granulysin levels significantly decreased in patients treated with tofacitinib compared to baseline (P = .001). The reduction in serum granulysin levels after tofacitinib therapy correlated with the reduction in SALT scores (P = .001). Conclusions Our results suggest serum granulysin levels to be a good correlate of immunological activity of AA. We also assume granulysin to be a potential mediator of follicle attack, the effects of which is blocked by tofacitinib therapy. Therefore, changes in serum granulysin levels under therapy can reflect the downregulation of immunological activity of AA.