Cellular autophagy and epithelial-mesenchymal transition (EMT) are key events mostly resulted from the interplay of tumor suppressors and oncogenes during cancer progression. The master tumor suppressor p53 may control tumor cell autophagy and EMT through the transcriptional induction of multiple target genes, while the activated oncogene RAS may also play a critical role in regulating mitogenic signaling to tumor cell autophagy and EMT. Although the fundamental functions of p53 and RAS are well understood, the interactive effects of p53 and RAS on autophagy and EMT are still unclear. In this review, we highlight the recent advances in the regulation of autophagy and EMT by p53 and RAS, aiming to explore novel therapeutic targets and biomarkers in cancer treatment and prevention.