•Combined effects of K1, K2,V1, V2, R*c1 and R*c2 are considered.•ETC is largely independent of R*c1/R*c2 when the R*c1 + R*c2 is less than 10−4.•ETC is not affected by the TC of filler-1 when K1 exceeds a critical value of 103.•The effect of Rc on ETC is influenced by K.•For each sum of Rc, there exists a critical value of R*c1/R*c2. There has been significant interest in enhancing the effective thermal conductivity (ETC) of polymer by incorporating spherical hybrid fillers. However, the effect of interface thermal resistance (Rc) on the ETC of composites has not been investigated. In this paper, this effect is investigated. Meanwhile, the combined effects of filler thermal conductivities (K1, K2), filler sizes (V1, V2), the Rc sum (R*c1 + R*c2) and the Rc ratio (R*c1/R*c2) are also considered. The results show that for a given K1, K2 and R*c1 + R*c2, the ETC is largely independent of R*c1/R*c2 when the R*c1 + R*c2 is less than 10−4. However, when the R*c1/R*c2 ranges from 10−2 to 10, the competing effects of hybrid fillers Rc have a significant effect on the ETC. The ETC is not affected by the TC of filler-1 when K1 exceeds a critical value of 103, instead becoming dependent on K2. For each sum of Rc, there exists a critical value of R*c1/R*c2 where the ETC reaches its nadir, this critical value is influenced by the R*c1 + R*c2, V and K of two fillers. The Rc of fillers with high K is <10−2, it is not feasible to improve the ETC by continuing to reduce its Rc, this value is 10−4 for fillers with low K.