Ni and Se co-doped skutterudite compounds Co1-xNixSb3-ySey with fine grains were fabricated by combining mechanical alloying and spark plasma sintering. The coupling effect between grain boundary scattering and point defect scattering on the thermoelectric transport properties was focused.The enhanced power factor by co_doping is twice that of the sample without Ni and achieved a maximum value of 1750μWm-1K-2 at 450℃ for x=0.1. Due to the coupling scattering effect, the lattice thermal conductivity at room temperature decreased to 1.67Wm-1K-1, which approach the reported minimum of 1.60Wm-1K-1, whareas the improved ZT value reached 0.53 at 450℃ for the Co0.9Ni0.1Sb2.85Se0.15. A suggested model shows that the decreased thermal conductivity is duc to the coupling effect between grain boundary scattering and point defect scattering, The calculated values are in good agreement with experimental results. The simulated results also suggest that the lattice thermal conductivity could be further decreased to 0.8Wm-1K-1 when the grain size was reduced to 50nm.