Some studies investigated the association between highly up-regulated in liver cancer (HULC) and the overall survival (OS) of cancer. However, the results were conflicted and inconclusive. Therefore, we performed this meta-analysis to determine the association between HULC and the OS of cancer. A comprehensive online search was conducted on Online electronic databases (PubMed, EMBASE, and Wanfang database) from the earliest date to Aug 30, 2016. The strength of the association was calculated with the HRs and respective 95% CIs. The expression of HULC was significantly associated with OS of cancers (HR = 2.12; 95% CI 1.61 - 2.79; P<0.00001). In the subgroup analysis by ethnicity, the expression of HULC was significantly associated with OS in Chinese patients (HR = 2.04; 95% CI 1.55 -2.70; P<0.00001). In the subgroup analysis by cancer type, HULC was associated with OS in osteosarcoma patients (HR = 3.36; 95% CI 1.02 - 11.07; P = 0.05) and in gastric cancer patients (HR = 2.17; 95% CI 1.08 - 4.38; P = 0.03). We performed the sensitivity analysis to assess the stability of the meta-analysis. A significant association was found in studies with adjustment (HR = 2.01; 95% CI 1.35 - 2.99; P = 0.0006). In conclusion, this meta-analysis suggested that high expression of HULC was significantly associated with OS of cancer.