Abstract Objective To evaluate the efficacy and safety of telitacicept in adult patients with primary SS (pSS) in a phase II randomized double-blind placebo-controlled trial. Methods Patients with pSS with positive anti-SSA antibody and ESSDAI ≥ 5 were randomly assigned, in a 1:1:1 ratio, to receive weekly subcutaneous telitacicept 240 mg, 160 mg, or placebo for 24 weeks. The primary end point was the change from baseline in the ESSDAI at week 24. Safety was monitored. Results A total of 42 patients were enrolled and randomized (n = 14 per group). Administration of telitacicept 160 mg resulted in a significant reduction in ESSDAI score from baseline to week 24 compared with placebo (P < 0.05). The placebo-adjusted least-squares mean change from baseline was –4.3 (95% CI –7.0, –1.6; P = 0.002). While, mean change of ESSDAI in telitacicept 240 mg was –2.7(–5.6–0.1) with no statistical difference when compared that in placebo group (P = 0.056). In addition, MFI-20 and serum immunoglobulins decreased significantly (P < 0.05) at week 24 in both telitacicept groups compared with placebo. No serious adverse events were observed in the telitacicept treating group. Conclusion Telitacicept showed clinical benefits and good tolerance and safety in the treatment of pSS. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT04078386