Midkine (MK) is a growth factor with cytokine action playing a central role in survival, growth, migration. The expression of MK is strictly controlled during embryogenesis that means high MK levels are detected in midgestation, but these levels were decreased after. MK regulates lung development, alveolar sacs formation and pulmonar vascular remodelling. Recent reports indicate that autophagy (lysosomal degradation pathway) is a tumor suppressor mechanism, which is connected to its role in the clearance of the scaffold protein, prevention of oxidative stress and genomic instability, however because autophagy is also expected as a survival mechanism, cancer cells can also exploit it to survive nutrient limitation and hypoxia. It was shown that hypoxia via hypoxia inducible factor-1 alpha enhanced the transcription of MK in developing lungs in vivo. Eventually, MK increased muscularization of small pulmonary arteries, increasing alpha-smooth muscle actin and caldesmon staining and the expression of myocardin, and consequently lung acquired a shape which they can function. MK involved in infammatory reactions and there is a complex reciprocal relationship between the autophagy pathway/proteins and immunity and inflammation; the autophagy proteins function in both the induction and suppression of immune and inflammatory responses, and immune and inflammatory signals function in both the induction and suppression of autophagy. In our recent study, we determined the significant role of MK in the switch from autophagy to apoptosis in human glioblastoma cells and spheroids. It can be speculated that MK determines the fate of autophagy as cell death or survival, or as the induction or supression of immune/inflamation responses.