In summary, this study linked the key enzyme of the sphingosine metabolism with the transcription factor PBX1 for the first time, and illustrated the potential regulatory role of the SPHK1/S1PR3/PBX1 axis in the cell cycle and a feedback interaction loop between PBX1 and S1PR3 in NSCLC. This evidence concerns the gene S1PR3 and non-small cell lung carcinoma.