Aim We sought to investigate the efficacy of adoptive transfer of TILs plus anti-PD1 therapy in metastatic osteosarcoma patients. Materials and methods A total of 30 patients received anti-PD1 therapy (Group 1) while 30 patients were subjected to TILs plus anti-PD1 therapy (Group 2). Progression-free survival time (PFS) and overall survival time (OS) were analyzed using Kaplan-Meier analysis. Potential prognostic factors were analyzed using univariate and multivariate analyses. Results The ORR in Group 2 is 33.3%, which is significantly higher than Group1 (6.67%). In addition, we found significantly prolonged mPFS (5.4 months) and mOS (15.2 months) in Group 2 compared to those in Group 1, which recorded mPFS and mOS of 3.8 and 6.6 months, respectively. Univariate and multivariate analyses indicate that patients with more infusions of TIL numbers and CD8+TILs or less infusions of CD8+ PD1+TILs and CD4+FoxP3+ TILs show increased PFS and OS. Moreover, PD1hi is another good prognostic factor that predict PFS and OS. Conclusion Overall, these findings indicated that TILs plus anti-PD1 therapy has significant clinical outcomes in metastatic osteosarcoma patients. However, further studies are essential to validate and characterize the therapeutic activity of TILs plus anti-PD1.