Electronic DNA sequencing using atomically thin 2D-based nanodevices has recently emerged as the next-generation of DNA sequencing technology. Recent molecular dynamics simulations showed that single-layer Titanium Carbide (Ti3C2) has a great potential for detecting individual DNA bases. In this work, we employ first-principles techniques based on density functional theory (DFT) to quantify the electronic interactions between the four DNA nucleobases (adenine, thymine, guanine, and cytosine) with 2D Ti3C2. Our results showed two distinct interaction mechanisms between DNA nucleobases and Ti3C2, namely, physisorption and chemisorption. Unlike graphene, where the binding energy for physisorption of DNA nucleobases is about 0.5 eV, we observe that the binding energy for physisorption for Ti3C2 is around 0.1 eV. This difference correlates to an increased distance between the nucleobases and the Ti3C2 (∼5.6 Å) compared to graphene (∼3.1 Å), indicating a weaker interaction. Based on these results, other electronic detection mechanisms, such as nanopore sequencing, would be worth exploring for Ti3C2.