Phycocyanin （PC） is a kind of natural food colorant with anti-cancer activity. Phycocyanin exerts significant inhibition effects on multiple tumors including lung cancer. However， the potential regulatory mechanism of phycocyanin in non-small cell lung cancer（NSCLC） cells is still unknown. In this study， we used three types of NSCLC cells （H1299， H460 and LTEP-a-2） as research model， and aimed to investigate the anti-proliferation and pro-apoptosis mechanism of phycocyanin in these cells. Cell phenotype experimental result indicated that phycocyanin could significantly inhibit the proliferation and induce apoptosis of H122， H460 and LTEP-a-2 cells. Transcriptome sequencing analysis on H1299 cells suggested that the expression of receptor interacting proteinkinase1（RIPK1） significantly downregulated after phycocyanin treatment. Knock-down expression of RIPK1 using siRNA could also decrease the proliferation and induce the apoptosis of H1299， H460 and LTEP-a-2 cells， which was consist with the phenotype results of phycocyanin. This study indicated that phycocyanin could inhibit proliferation and induce apoptosis of multiple non-small cell lung cancer cells through down-regulating RIPK1， which provided important theoretical basis for the development and utilization of natural functional food additives， also provided useful information on the treatment of non-small cell lung cancer.