In the present study, we demonstrate for the first time that SGK1, acting through SP1-dependent transcriptional and functional regulation of RANBP1 and RANGAP1, affects the binding status of GTP/GDP of RAN as well as RANBP1/RANGAP1 protein abundance and the localization of XPO5, thus enhancing the nuclear export and maturation of pre-miRNAs, without significantly affecting pri-miRNA levels, in a cellular model of HCC and in several neoplastic and non-tumoral primary cell lines. This evidence concerns the gene RANBP1 and hepatocellular carcinoma.