Background: Antiangiogenesis therapy combined with PD-1/PD-L1 inhibitors has shown excellent efficacy in advanced refractory solid tumors. In advanced NSCLC patients,this conclusion has been confirmed in a number of clinical studies such as WJOG@Be Study and JVDF. A clinical study, KEYNOTE-524/Study116, demonstrated survival benefits from this combination model in liver cancer, and a similar trend was seen in patients in the bile duct cancer study presented.Penpulimab + anlotinib is an important combination immunotherapy. Here we described the results of safety, and clinical efficacy of penpulimab combined with anlotinib in patients with advanced solid tumors, the serum cytokine levels, and peripheral blood T lymphocyte populations were detected simultaneously. Methods: 17 cases with advanced cancers including lung, gallbladder, cholangiocarcinoma, and hepatocellular Carcinoma were treated since January 2022. Patients received a combination of anlotinib (12mg) once daily on day 1 to day 14 (21days as a course) plus anti-PD-1 antibodies every 3 weeks until progression or intolerabletoxicity. Imaging was performed every 6 weeks for thefirst year of therapy. Blood samples were collected from patients prospectively. Serum interleukin (IL-2, IL-4, IL-6, IL-10), tumornecrosis factor-α(TNF-α), interferon-γ(IFN-γ) and circulating immune cell subsets were measured at baseline and after two cycles of treatment via flow cytometry. Results: From January 2022 to December 2022, 17 patients had received the combination therapy of penpulimab plus anlotinib (median age 68.8yrs [range 51-83],52.9% males, 100% ECOG PS 1. Most patients had received frist line treatments for metastatic disease (82.4%). Of 13 pts who have had at least one tumor assessment, the ORR（objective remission rate ）was 35.29% (6 PRs) and DCR was 58.82% (4 SDs). The median PFS was 7.98 months (95% CI: 1.68-NE months).Up to now, eight responders remain in response.The most common adverse reactions included：hypertension was 1/17（5.9%）, Hand foot syndrome was 1/17（5.9%）, loss of appetite was 1/17（5.9%）.There were no grade 3 and above treatment-related adverse events. Conclusions: The combination of penpulimab plus anlotinib as a treatment for advanced refractory solid tumor showed the promising efficacy with a manageable safety profile, thereby suggesting that this combination therapy may be a viable treatment strategy for advanced refractory solid tumor patients.