Spherical nano-MoS₂ (S-MoS₂) has excellent lubricating properties and potential application value in engine oil additives. Engine soot can enter the engine oil, so the tribological interaction between S-MoS₂ and diesel combustion soot (DCS) should be investigated. In this study, DCS was used to simulate engine soot. The interaction was investigated in dioctyl sebacate (DOS), and the interaction mechanism was full characterized. Results showed that S-MoS₂ and DCS had obvious antagonism effects on lubrication. The 0.5% S-MoS₂ exhibited good lubricating properties in DOS, which could reduce friction by ~22% and wear by ~54%. However, after 0.5% S-MoS₂ was added to the 0.5% DCS contaminated DOS, the lubrication performance was not improved and was even worse than that without S-MoS₂. When S-MoS₂ was added for DOS lubrication, a tribofilm containing MoS₂ formed on the friction surface, but simultaneously adding 0.5% DCS resulted in the disappearance of the MoS₂ tribofilm. Moreover, under the action of friction heat, DCS and S-MoS₂ could form hard Mo_xC_y, thereby increasing abrasive wear. Finally, a preliminary deantagonism method was provided. After 2.0% zinc isooctyl dithiophosphate was added to the above antagonistic system, the friction coefficient did not show visible changes, but the wear recovered to a level close to that when only S-MoS₂ was added. The antiantagonism method is not very satisfactory and some more efficient methods need to be further explored.