Si micromolds are common for fabrication of polymer-based microfluidic devices by hot-embossing because of the well established fabrication methods for Si, e.g., deep reactive ion etching, for favorable surface finish and accuracy. The problems with low yield, poor reproducibility, premature failure and limited lifetime of a Si micromold are induced by high friction and surface adhesion generated during demolding. Therefore, Titanium (Ti) and molybdenum disulfide (MoS2) coatings were deposited on Si micromolds via magnetron co-sputtering at various combinations of target powers to improve its surface properties. Coating composition, crystallographic orientation, roughness, critical load, hardness, friction coefficient and surface energy were measured by X-ray photoelectron spectroscopy, X-ray diffraction, atomic force microscopy, scratch testing, nanoindentation, ball-on-disc tribometry and the contact angle method respectively. A statistical design of experiment matrix was used to investigate the effect of the Ti and MoS2 target powers on the friction coefficient and surface energy of the coatings. From this designed experiment, it was observed that increasing MoS2 target power was associated with increasing surface energy and decreasing friction coefficient and target powers had statistically significant effects on these parameters. Crystallinity, roughness and hardness of the coatings increased with increasing Ti concentration. A mathematical model of the effects of Ti and MoS2 target powers on the friction coefficient and surface energy of the coatings has been fit to the experimental results using the response surface method. Uncoated and MoS2–Ti coated Si micromolds were used in hot-embossing for a comparative study on replication performance of uncoated and various coated micromolds. Hotembossed PMMA microstructures showed that coating improve replication performance of Si micromolds. Si micromold coated with co-sputter of Ti and MoS2 at power of 300 and 75 W respectively, showed better replication quality among the selected target powers.