Identification of long non-coding RNAs (lncRNAs) has provided a substantial increase in our understanding of the non-coding transcriptome. Studies have revealed a crucial function of lncRNAs in the modulation of cell autophagy in vitro and in vivo, further contributing to the hallmarks of disease phenotypes. These findings have profoundly altered our understanding of disease pathobiology, and may lead to the emergence of new biological concepts underlying autophagy-associated diseases, such as the carcinomas. Studies on the molecular mechanism of the lncRNA-autophagy axis may offer additional avenues for therapeutic intervention and biomarker assessment. In this review, we discuss recent findings on the multiple molecular roles of regulatory lncRNAs in the signaling pathways of cell autophagy. The emerging knowledge in this rapidly advancing field will offer novel insights into human diseases, especially cancers.