Thermal issues have become increasingly important for the performance and lifetime of highly miniaturized and integrated devices. However, the high thermal resistance across the polymer/semiconductor interface greatly weakens the fast heat dissipation. In this study, applying the self-assembled monolayer (SAM) technique, organic molecules are employed as heat regulators to mediate interfacial thermal conductance (ITC) between semiconductors (silicon or Si) and polymers (polystyrene or PS). Silane-based SAM molecules with unique functional groups, such as –NH₂, –CH₃, –SH, and –Cl, are orderly assembled into Si–PS interfaces. Their roles in ITC and the heat transfer mechanism were systematically investigated. Molecular simulations demonstrate that the Si–PS interface decorated with SAM molecules can significantly facilitate heat transfer in varying degrees. Such a difference is primarily due to the different non-bonded interactions and compatibility between SAMs and PS. Compared with the pristine Si–PS interface, the interface incorporated with 3-chloropropyl trimethoxysilane shows the greatest improvement in ITC, about 507.02%. Such improvements are largely attributed to the SAM molecules, as the thermal bridges straighten the molecular SAM chains, develop strong non-bonded interactions with PS, provide the covalent bonding between Si and PS, exhibit a strong coupling effect between two materials’ vibrational modes, and eliminate the discontinuities in the temperature field. Eventually, these demonstrations are expected to offer molecular insights to enable effective thermal management through surface engineering for critical-heat transfer materials and microelectronic devices.