Background: Eribulin combined with a multi-targeted antiangiogenic tyrosine kinase inhibitor has shown efficacy in STS. ICIs have also exhibited improved survival in some STS subtypes. We investigated the efficacy and safety of triple combination therapy with eribulin, an ICI and anlotinib in the treatment of advanced STS in an adult Chinese population. Methods: This study retrospectively analyzed data from patients diagnosed with advanced STS who received combination therapy with eribulin, an ICI and anlotinib at the Department of Oncology, Zhongshan Hospital affiliated to Fudan University. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) by RECIST v1.1, disease control rate (DCR), and treatment-related adverse events (TRAEs) by CTCAE v5.0. Results: Medical records from 32 pts treated between August 15, 2020 and January 31, 2023 were included; the median age was 56 years, 71.8% (23/32) were female, 75.0% (24/32) had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, and 25.0% (8/32) had an ECOG PS of 2. Pts had received a median of 2 (range 0-6) prior regimens and the median follow-up was 4.1 months. Among the patients, 50.0% (16/32) had liposarcomas (including 1 with pleomorphic liposarcoma and 15 with dedifferentiated liposarcoma [DDLPS]), 31.3% (10/32) had leiomyosarcomas (LMS), 3 had undifferentiated pleomorphic sarcoma (UPS), and 1 each had angiosarcoma, rhabdomyosarcoma and desmoplastic small round cell tumor. In a preliminary analysis, 29 pts were evaluable for clinical activity; partial responses (PRs) were achieved in 3 pts (2 DDLPS, 1 UPS), the ORR and DCR were 10.3% (3/29) and 62.1% (18/29) respectively, and the median PFS was 5.7 months (95% CI 2.7-9.8). Of the 15 pts with DDLPS (median 1 prior line of therapy; median follow-up 6.3 months), 13 were evaluable for clinical activity; a PR was achieved by 15.4% (2/13), the DCR was 61.5% (8/13), the median PFS was 9.8 months (95% CI 1.8-28.5) and treatment was ongoing in 46.7% of pts (n = 7). Among the 9 evaluable pts with LMS, 0 achieved a PR, the DCR was 44.4% (4/9), median PFS was 3.9 months and 3 pts were still receiving treatment. In the overall cohort (n = 32), TRAEs of any grade occurred in 56.3% of pts (n = 18), the most common were myelosuppression (28.1%), fatigue (15.6%), fever (12.5%) and rash (12.5%). Grade 3/4 TRAEs occurred in 12.5% of pts, with no grade 5 events. Conclusions: This study demonstrates the potential efficacy of combination therapy with eribulin, an ICI and anlotinib in patients with advanced STS, especially in those with the DDLPS subtype. Our data suggest that this combination has good tolerability and a prospective trial is warranted. Clinical trial information: ChiCTR2100053594.