Advances in patient care for pressure injuries (PIs) have reduced the prevalence of PIs in Japan, although not in recent years. Several single-nucleotide polymorphisms (SNPs) have been identified in genes potentially associated with PIs. However, individual variance among PI risks require targeted investigations that may lead to the identification of PI susceptibilities or preventive care options that directly influence PI development pathways. This cross-sectional study examined the association between PIs and SNPs in genes related to tissue tolerance in patients in a long-term care hospital in Japan. A total of 178 participants (130 control, 20 with superficial PI history, and 28 with deep PI history) were enrolled in this study of eight SNPs in hypoxia inducible factor 1 subunit alpha (HIF1A), vascular endothelial growth factor C (VEGFC), heat shock protein 90 alpha family class A member 1 (HSP90AA1), myostatin (MSTN), and vitamin D receptor (VDR). The primary outcome was a history of superficial and deep PIs in the last 6 months. SNPs were examined by real-time polymerase chain reaction, followed by multivariate logistic regression analyses of the associations between the SNPs and PI history. The results showed a significant association between VEGFC rs1485766 and the history of superficial PIs (odds ratio = 2.95; 95% confidence interval = 1.07-8.11; p = 0.04). Stratified analysis using the Braden Scale (≤14) indicated a significant association between HIF1A rs11549465 and deep PIs (p = 0.04). Our study demonstrated that VEGFC rs1485766 and HIF1A rs11549465 were associated with superficial and deep PI susceptibilities, respectively.