The HgTe quantum well (QW) is a well-characterized two-dimensional topological insulator (2D-TI). Its band gap is relatively small (typically on the order of 10 meV), which restricts the observation of purely topological conductance to low temperatures. Here, we utilize the strain-dependence of the band structure of HgTe QWs to address this limitation. We use CdTe-Cd0.5Zn0.5Te strained-layer superlattices on GaAs as virtual substrates with adjustable lattice constant to control the strain of the QW. We present magneto-transport measurements, which demonstrate a transition from a semimetallic to a 2D-TI regime in wide QWs, when the strain is changed from tensile to compressive.Most notably, we demonstrate a much enhanced energy gap of 55 meV in heavily compressively strained QWs. This value exceeds the highest possible gap on common II-VI substrates by a factor of 2-3, and extends the regime where the topological conductance prevails to much higher temperatures.The transport properties of molecular-beam epitaxially (MBE) grown HgTe QWs embedded in Cd 0.7 Hg 0.3 Te barriers have attracted considerable attention due to the discovery of the quantum-spin-Hall (QSH) effect in these structures [1][2][3]. The QSH effect is the landmark property of a 2D-TI and is characterized by the presence of a pair of one-dimensional, counter-propagating ("helical") channels along the edges of the mesa, giving rise to a quantized longitudinal conductanceA prerequisite for the formation of edge channels is atopologically nontrivial -inverted band structure, as is present in HgTe QWs when the thickness d QW exceeds d c = 6.3 nm [1]. Inverted HgTe QWs have a relatively small band gap E G (typically lower than 15 meV), which can make it difficult to gate homogeneously into the gap over the whole mesa, and also prevents applications at elevated temperatures. Here we present a way to increase E G well above the thermal energy at room temperature (k B T = 25 meV). This is achieved by applying compressive strain to HgTe QWs through coherent growth on virtual substrates with a freely tunable lattice constant.The crucial influence of strain on the band structure of HgTe has been demonstrated previously for bulk layers (layer thickness d > 40 nm): epitaxy of HgTe on CdTe substrates exerts tensile strain (ε = −0.3 %), which causes a gap-opening of the Γ 8 doublet, transforming the bulk semimetal into a three-dimensional topological insulator [4,5]. However, these previous experiments used commercially available MBE quality substrates, limiting the options to Cd 0.96 Zn 0.04 Te[1-3] and CdTe [4,5][6]. In both cases, the lattice constant of the substrate material is larger than that of HgTe, resulting in a tensile strain in the epilayers. Under such conditions, the largest gaps that can be obtained in inverted QWs are E G = 17 meV and 25 meV for wells grown on CdTe and Cd 0.96 Zn 0.04 Te, respectively [7].The present work reports on a major progress in this situation. We use CdTe-Cd 0.5 Zn 0.5 Te (001) strainedlayer superlattices (SLS) as virtual ...