Pancreatic cancer constitutes the fourth most frequent cause of death due to malignancy in the US. Despite the new therapeutic modalities, the management of pancreatic ductal adenocarcinoma (PDAC) is considered a difficult task for clinicians due to the fact that is usually diagnosed in already advanced stages and it is relatively resistant to the current chemotherapeutic agents. The molecular background analysis of pancreatic malignant tumors, which includes various epigenetic and genetic alterations, opens new horizons for the development of novel diagnostic and therapeutic strategies. The interplay between miRNAs, autophagy pathway, and pancreatic carcinogenesis is in the spotlight of the current research. There is strong evidence that miRNAs take part in carcinogenesis either as tumor inhibitors that combat the oncogene expression or as promoters (oncomiRs) by acting as oncogenes by interfering with various cell functions such as proliferation, programmed cell death, and metabolic and signaling pathways. Deregulation of the expression levels of various miRNAs is closely associated with tumor growth, progression, and dissemination, as well as low sensitivity to chemotherapeutic agents. Similarly, autophagy despite constituting a pivotal homeostatic mechanism for cell survival has a binary role in PDAC, either as an inhibitor or promoter of carcinogenesis. The emerging role of miRNAs in autophagy gets a great deal of attention as it opens new opportunities for the development of novel therapeutic strategies for the management of this aggressive and chemoresistant malignancy. In this review, we will shed light on the interplay between miRNAs and the autophagy mechanism for pancreatic cancer development and progression.