A combination of two passive heat transfer enhancement techniques using a microfin structure and nanofluids was investigated numerically. TiO2/water nanofluids flowing inside a square minichannel with a microfin structure (SMM) were observed as a practical application. Increased heat transfer performance was investigated by observing the Nusselt number, friction factor, and performance evaluation criterion (PEC). Velocity and temperature profiles were also demonstrated at a laminar developing flow regime. The SMM used in this work had six microfins (N = 6) and TiO2/water nanofluids with various nanoparticle concentrations of 0.005, 0.01, and 0.1 vol.%. By combining nanofluids as working fluids and SMM as a passive heat transfer enhancement, the maximum PEC value of 1.2 was achieved at Re = 380 with a volume fraction of 0.01 vol.%. It is obvious that compared to water flowing inside the square minichannel microfin, the heat transfer can be increased by using only a nanofluid with a volume fraction of 0.01%. The combination of a microfin and nanofluids as working fluids is strongly recommended due to its excellent performance in terms of heat transfer and economic considerations.