Glycine decarboxylase (GLDC) belongs to the glycine cleavage system and is involved in one-carbon metabolism. We previously reported that GLDC downregulation enhances hepatocellular carcinoma (HCC) progression and intrahepatic metastasis through decreasing ROS-mediated ubiquitination of cofilin. The role of autophagy in cancer metastasis is still controversial. Redox-dependent autophagy largely relies on the magnitude and the rate of ROS generation. Thus, we aimed to explore the role of GLDC in cellular autophagy during HCC progression. We showed that a high GLDC expression level is associated with better overall survival and is an independent factor for the favorable prognosis of HCC patients. GLDC overexpression significantly induced cell autophagy, whereas GLDC downregulation reduced cell autophagy. Of note, GLDC is the post-transcriptional target of miR-30d-5p. GLDC overexpression could rescue miR-30d-5p-mediated cell metastasis and increase autophagy. Furthermore, upregulation of GLDC could significantly decrease p62 expression and impair intrahepatic metastasis in vivo. Taken together, our results suggest that GLDC may play an important role to increasing miR-30d-5p-reduced autophagy to suppress HCC progress.