Phycocyanin (PC) is a kind of natural pigment protein complex derived from marine algae. It is also a type of important food functional factor with anti-cancer， anti-inflammatory， and immune-enhancing activities， and has been widely used in functional food， medicine and cosmetics. Phycocyanin has been proven to inhibit the activity of non-small cell lung cancer (NSCLC) cells， but the underlying regulatory mechanism is not fully understood. This study focused on miR-642a-3p， and investigated the potential regulating mechanism of phycocyanin in NSCLC cells. The results showed that phycocyanin upregulated the expression level of miR-642a-3p in four NSCLC cells(A549， H1299， H460 and LTEP-a2). Overexpression of miR-642a-3p levels significantly inhibited the proliferation， migration and unanchored growth of four cells in vitro. In addition， transfection of miRNA inhibitors to interfere with the expression of miR-642a-3p could enhance cell viability to a certain extent. This study preliminarily revealed that the up-regulation expression of miR-642a-3p was involved in the regulation of inhibiting NSCLC cell viabilities by phycocyanin， which could lay a scientific theoretical basis for the in-depth study and utilization of phycocyanin.