Similar to the biological behaviors of these tiny noncoding RNAs, several specific miRNAs bind to the HMGB1 mRNA, via the particular targeting effect of the “seed” region of miRNAs in the coding region and 3′ UTR of the mRNA, thus guiding the process of HMGB1 mRNA degradation, influencing downstream signal pathways, such as HMGB1-RAGE-MMP2/MMP9 signaling [40], and ultimately altering the malignant tumor characteristics of HCC (Figure 1). This evidence concerns the gene HMGB1 and neoplasm.