Emerging evidence has revealed that dysregulation of lncRNAs correlate with the development and progression of hepatocellular carcinoma (HCC). In the present study, we globally investigated the expression of SNHG6 in 31 cancer type, and we found that SNHG6 was highly expressed in various cancers, especially in HCC. High expression of SNHG6 was associated with progression and poor prognosis in patients with HCC. Gain of function and loss of function assays showed that SNHG6 promoted HCC cell proliferation. Gene Set Enrichment Analysis (GSEA) and correlation analysis suggested that SNHG6 positively correlated with c-Myc and its downstream targets. Ectopic overexpression of SNHG6 markedly increased the expression of c-Myc and its downstream targets, whereas silencing SNHG6 had the opposite effect on the expression of c-Myc and its downstream targets. Mechanistic assays revealed that SNHG6 acted as a competing endogenous RNA (ceRNA) to sponge let-7c-5p and thereby modulating the depression of c-Myc by let-7c-5p. Taken together, SNHG6 promotes HCC cell proliferation via competitively binding let-7c-5p in hepatocellular carcinoma. (C) 2019 Elsevier Inc. All rights reserved.