Modified carbon nanotube/nano-MoS2 (CMS) hybrid as a self-lubricating and anti-wear nanofiller was prepared through chemical compounding and then incorporated into polyimide (PI) matrix to yield CMS/PI composite by in situ polymerization. For comparison, carbon nanotube (CNT), nano-MoS2 as well as the mixture of them (CNT-MoS2) were also incorporated into PI matrix separately to evaluate the superior performance of CMS hybrid. Morphology, mechanical capacity and tribological behavior of the as-prepared nanocomposites were investigated, and the discrepancies on the above-mentioned properties caused by the different structures between CMS hybrid and CNT-MoS2 mixture were discussed in detail. With only 0.5 wt% addition of CMS, the friction coefficient and wear rate of CMS/PI composite decreased by 31 and 84%, respectively, compared to virgin PI. The results showed that the combinational structure of CMS hybrid, as CNT-coated few-layer-MoS2 nanosheet, which took the advantage of both CNT and nano-MoS2, contributed to the synergistic effect on the tribological properties.