Bcl-2 is an important gene of apoptosis research, during the past decade, there has been an increasing interest in the relationship between Bcl-2 and the apoptosis, but only a few studies talk about the relationship between Bcl-2 and propofol, which is a wild use narcotic that can protect cells against various injuries. In the present study, we showed that propofol could down-regulate miR-297a-5p to increased Bcl-2 level. We think this might be a possible mechanism of propofol protecting cell from death. Furthermore, we use an apoptotic drug staurosporine to further improve the propofol's cell protecting function by showing that propofol prevented neurons against staurosporine. Our study supplies a possible mechanism that propofol could regulating Bcl-2 level through miRNA to protect cells.