Chain initiation reactions in the oxidation process of lubricant base stock molecules were studied by molecular simulations. Two ways to initiate lubricant oxidation were investigated. They included the dissociation of chemical bonds in base stock molecules and the reaction between base stock molecules and oxygen (O2), respectively. Reaction activation energy of above methods was calculated. The results show that C?C bonds are more likely to break than C?H bonds to generate free radicals by the pyrolysis of chemical bonds. The C?C bonds with tertiary carbon atoms are preferential positions to crack. However, their bond dissociation energy is above 360 kJ/mol, which is difficult to occur under lubricant working conditions. The chain initiation is more likely to occur by the way that O2 attacks the two atoms in C?H bonds at the same time, and is then embedded into the C?H bond to produce hydrocarbon peroxides. And then, the O?O bond is cracked to form hydroxyl radicals and alkoxy radicals. The C?H bonds with tertiary carbon atoms are preferential reaction sites, the reaction activation energy of which is about 190.11 kJ/mol.