How single nucleotide polymorphisms in long non-coding RNAs are involved in cancer susceptibility remains poorly understood. We hypothesized that polymerase II polypeptide E (POLR2E) rs3787016 polymorphism, identified in a genome-wide association study of prostate cancer, might be a common genetic risk factor for cancer risk. To address this issue, we here conducted a case–control study to investigate the association of POLR2E rs3787016 polymorphism with risk of liver and lung cancer (including 800 normal controls, 480 liver cancer patients, and 550 lung cancer patients), followed by a meta-analysis. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. Although no significant association was found for rs3787016 with risk of liver or lung cancer, the further stratified analysis identified that rs3787016 contributed to liver cancer risk particularly for over than 60 years individuals who drink. Moreover, the meta-analysis demonstrated that rs3787016 was associated with overall cancer risk and prostate cancer risk. Collectively, the POLR2E rs3787016 polymorphism may be a valuable biomarker for cancer predisposition.