Surface‐anisotropic nanoparticles represent a new class of materials that shows potential in a variety of applications, including self‐assembly, microelectronics, and biology. Here, the first synthesis of surface‐anisotropic silicon quantum dots (SiQDs), obtained through masking on 2D silicon nanosheets, is presented. SiQDs are deposited on the 2D substrate, thereby exposing only one side of the QDs, which is functionalized through well‐established hydrosilylation procedures. The UV‐sensitive masking substrate is removed through UV‐irradiation, which simultaneously initiates the hydrosilylation of a second substrate, thereby introducing a second functional group to the other side of the now free‐standing SiQDs. This renders surface‐anisotropic SiQDs that have two different functional groups on either side of the particle. This method can be used to introduce a variety of functional groups including hydrophilic and hydrophobic substrates, while the unique optoelectronic properties of the SiQDs remain unaffected. The anisotropic morphology of the QDs is confirmed through the aggregation behavior of amphiphilic Janus SiQDs at the interface of water and hexane. Additionally, anisotropic SiQDs are used to produce the first controlled (sub)monolayer of SiQDs on a gold wafer.