Recently, we reported that the expression of SPRED2, an endogenous MAPK/ERK inhibitor, was downregulated in human HCC [8] and the transcription of p62 is regulated by the MAPK/ERK pathway [15]; therefore, the negative association of SPRED2 with p62 was of particular interest and served as the basis for our investigation of the intricate interactions and potential functional implications of SPRED2 within the autophagy pathway. This evidence concerns the gene SQSTM1 and hepatocellular carcinoma.