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<b>Objective</b> To elucidate the role and prognostic significance of lymphocyte activation-gene-3 (LAG-3) in soft tissue sarcoma (STS).<b>Methods</b> The expression of LAG-3 in patient and matched normal blood samples was analyzed by flow cytometry. The localization and prognostic values of LAG-3⁺ cells in 163 STS patients were analyzed by immunohistochemistry. In addition, the expression of tumor-infiltrating CD3⁺ T, CD4⁺ T, and CD8⁺ T cells and their role in the prognosis of STS were evaluated by immunohistochemistry. The effect of LAG-3 blockade was evaluated in an immunocompetent MCA205 fibrosarcoma mouse model.<b>Results</b> Peripheral CD8⁺ and CD4⁺ T cells from STS patients expressed higher levels of LAG-3 than those from healthy donors. LAG-3 expression in STS was significantly associated with a poor clinical outcome (<i>P</i> = 0.038 ) and was correlated with high pathological grade (<i>P</i> &lt; 0.001), advanced tumor stage (<i>P</i> = 0.016). Additionally, LAG-3 expression was highly correlated with CD8⁺ T-cell infiltration (<i>r</i> = 0.7034, <i>P</i> &lt; 0.001). LAG-3 was expressed in murine tumor-infiltrating lymphocytes, and its blockade decreased tumor growth and enhanced secretion of interferon-gamma by CD8⁺ and CD4⁺ T cells.<b>Conclusions</b> LAG-3 blockade may be a promising strategy to improve the effects of targeted therapy in STS.