Phosphoinositides (PIs) play an essential role in mediating key signaling pathways on biological membranes. Hepatitis C virus (HCV) replicates its RNA genome by establishing a viral replication complex (RC) on host cell membranes. Recently, an increasing body of literature reported that not only PIs themselves but also several PIs-specific kinases are required for efficient replication of HCV RNA genome. Especially, PI 4-kinases type III alpha, beta as well as their enzymatic products including phosphatidylinositol 4-phosphate (PI(4)P) and phosphatidylinositol 4,5-bisphosphate (PI(4,5)$P_2$) are consistently identified to be host factors essential for HCV replication. In this article, the current state of our knowledge of PIs and PIs-specific kinases together with their roles in modulating HCV replication is reviewed. The effects of various PIsspecific kinases inhibitors on HCV replication are also highlighted, proposing them as promising candidate targets to which a new class of anti-HCV therapeutics can be envisaged.