Lactate dehydrogenase 5 (LDH5) is believed to be particularly important and a reliable marker of malignancy. However, it is still controversial whether LDH5 expression can be regarded as a prognostic factor for cancer patients. We reviewed the literature by performing an electronic database search via PubMed to identify eligible studies that assessed the impact of LDH5 as a cancer prognostic marker and its association with HIF-1α. Heterogeneity and publication bias were also assessed. A total of 12 literatures which included 1,892 cancer patients were combined in the final analysis. Meta-analysis revealed that LDH5 overexpression was associated with an unfavorable overall survival (12 studies, 1,597 patients; HR 1.59, 95 % CI 1.17-2.16) and disease/recurrence/progression-free survival (7 studies; 1,086 patients; HR 1.46, 95 % CI 1.04-2.04) among solid tumor patients. Meta-analysis revealed an association between the expression of LDH5 and hypoxia-inducible factors 1 (OR 2.72, 95 % CI 1.66-4.45). Publication bias could not be excluded when investigating the association of LDH5 expression and overall survival. However, when we accounted for publication bias using the trim and fill method, the results remained significant (HR 1.435, 95 % CI 1.071-1.923, P < 0.05) suggesting the stability of our results. Therefore, our study suggested that LDH5 overexpression had a poor prognosis value in cancer patients. The results of this meta-analysis suggest that high LDH5 expression is associated with HIF-1α and poor overall survival in cancer patients.