mxd = arcpy.mapping.MapDocument("current") #or provide full path to MXD
df = arcpy.mapping.ListDataFrames(mxd, "df name") #replace with actual df name
lyr = arcpy.mapping.ListLayers(mxd, "MyShapeFileLayer")[0] #replace with acutal layer name in TOC
arcpy.mapping.RemoveLayer(df, lyr)
mxd.save()