Lactate dehydrogenase A (LDHA), a critical enzyme involved in glycolysis, is broadly involved multiple biological functions in human cancers. It is reported that
LDHA
can impact tumor immune surveillance and induce the transformation of tumor-associated macrophages, highlighting its unnoticed function of
LDHA
in immune system. However, in human cancers, the role of
LDHA
in prognosis and immunotherapy hasn’t been investigated. In this study, we analyzed the expression pattern and prognostic value of
LDHA
in pan-cancer and explored its association between tumor microenvironment (TME), immune infiltration subtype, stemness scores, tumor mutation burden (TMB), and immunotherapy resistance. We found that
LDHA
expression is tumor heterogeneous and that its high expression is associated with poor prognosis in multiple human cancers. In addition,
LDHA
expression was positively correlated with the presence of mononuclear/macrophage cells, and also promoted the infiltration of a range of immune cells. Genomic alteration of
LDHA
was common in different types of cancer, while with prognostic value in pan-cancers. Pan-cancer analysis revealed that the significant correlations existed between
LDHA
expression and tumor microenvironment (including stromal cells and immune cells) as well as stemness scores (DNAss and RNAss) across cancer types. Drug sensitivity analysis also revealed that
LDHA
was able to predict response to chemotherapy and immunotherapy. Furthermore, it was confirmed that knockdown of
LDHA
reduced proliferation and migration ability of lung cancer cells. Taken together,
LDHA
could serve as a prognostic biomarker and a potential immunotherapy marker.