The use of immunotherapy as a subsequent treatment for thymic carcinoma remains controversial due to efficacy indications and safety concerns, particularly immune-related adverse events observed with PD-1 inhibitors. This study presents the results from the first interventional trial of PD-L1 inhibitor atezolizumab in pretreated thymic carcinoma patients. The efficacy data aligns with historical benchmarks, showing particularly promising results in PD-L1-positive patients. Safety risks were acceptable, with no new safety signals observed. Introduction: There are limited treatment options for thymic carcinoma. This study aimed to evaluate the efficacy and safety of atezolizumab for the treatment of advanced thymic carcinoma after failure with prior systemic therapy. Patients and Methods: Patients aged >_ 18 years with advanced thymic carcinoma after failure with prior systemic therapy were enrolled at 10 medical centers in China. Atezolizumab 1200 mg was administered on Day 1 (baseline) every 3 weeks until unacceptable toxicity/loss of clinical benefit. The primary efficacy endpoint was the confirmed objective response rate in the full analysis set. Results: Between 29 July 2020 and 28 December 2022, 34 patients enrolled (median age, 54.5 years), and 16 (47.1%) had received >_ 2 prior lines of therapy. At the cut-off date (July 16, 2023), the median follow-up duration was 19.1 months. The confirmed objective response rate (ORR) was 14.7% (95% confidence interval, 5.0%31.1%); disease control rate, 58.8%; median progression-free survival (PFS), 3.2 months; 24-month OS rate, 63.2%; Better ORR and PFS were observed in PD-L1-positive patients versus PD-L1-negative patients (40.0% vs. 0% and 7.4 vs. 1.5 months, respectively). No correlation was observed with TMB. The incidence of adverse events (AEs) was 94.1%; serious AEs, 26.5%; immune-related AEs, 29.4%; and AEs leading to drug withdrawal, 2.9%. Conclusions: In patients with advanced thymic carcinoma who had failed prior systemic therapy, atezolizumab was well-tolerated with a manageable toxicity profile and showed encouraging the antitumor activity, especially in patients with PD-L1-positive tumors.