Background: Identification of modulators of the immune response with inhibitory properties that could be susceptible for therapeutic intervention is a key goal in cancer research. An example is the human leukocyte antigen G (HLA-G), a nonclassical major histocompatibility complex (MHC) class I molecule, involved in cancer progression. Methods: We performed a systematic review and meta-analysis on the role of HLA-G expression and outcome in solid tumors. A total of 25 studies met the inclusion criteria comprising data from 4871 patients reporting overall survival (OS) outcomes, and 961 patients, in 5 studies, for disease free survival (DFS). This study was performed in accordance with PRISMA guidelines and registered in PROSPERO. Results: HLA-G expression was associated with worse OS (HR 2.09, 95% CI = 1.67 to 2.63; P < .001), that was higher in gastric (HR = 3.40; 95% CI = 1.64 to 7.03), pancreatic (HR = 1.72; 95% CI = 0.79 to 3.74) and colorectal (HR = 1.55; 95% CI = 1.16 to 2.07) cancer. No significant differences were observed between the most commonly utilized antibody (4H84) and other methods of detection. HLA-G expression was associated with DFS which approached but did not meet statistical significance. Conclusions: We describe the first meta-analysis associating HLA-G expression and worse survival in a variety of solid tumors.