Porcine deltacoronavirus (PDCoV) is an important enteric pathogen of piglets, yet the host factors that restrict its infection remain poorly understood. Tetratricopeptide repeat domain 7A (TTC7A) is a scaffold protein involved in intestinal epithelial function and membrane-associated cellular processes, but its role in PDCoV infection is unknown. Here, we investigated the role of TTC7A and its association with the PDCoV spike protein through tissue expression analysis, gain- and loss-of-function experiments, co-immunoprecipitation, structure-guided prediction, and site-directed mutagenesis. TTC7A was expressed at approximately 4–5-fold higher levels in porcine intestinal tissues, the principal sites of PDCoV infection, than in muscle. Functional analyses showed that TTC7A overexpression (approximately 3-fold higher protein levels) suppressed PDCoV infection, whereas RNA interference-mediated knockdown enhanced infection by approximately 30% relative to the control, demonstrating that endogenous TTC7A restricts PDCoV infection. Co-immunoprecipitation assays further revealed an association between TTC7A and the C-terminal domain of the PDCoV spike protein. Structure-guided analysis identified candidate residues at the interaction interface, and site-directed mutagenesis of these residues impaired the TTC7A-spike interaction (a decrease of approximately 46%), supporting their contribution to this association. Together, these findings identify TTC7A as a host restriction factor for PDCoV and characterize its interaction with the viral spike protein. This study expands our understanding of host-mediated restriction of PDCoV and provides a basis for determining how TTC7A-spike association contributes to its antiviral activity.