Background <p>Psychological stress and financial hardship are long-standing issues for patients with primary liver cancer. Financial toxicity levels are closely related to quality of life, and resilience is a key psychosocial resource for maintaining quality of life.</p> Objective <p>The purpose of this study was to explore the relationship between resilience, financial toxicity, and quality of life.</p> Methods <p>This cross-sectional study included 268 patients with primary liver cancer between July and December 2023. CD-RISC, COST-PROM, and QOL-LC were used to identify patients’ resilience, financial toxicity, and quality of life. Univariate and multivariate analyses examined factors associated with quality of life, and Pearson’s correlation analysis was used to analyze the relationship between the three scales. Subsequently, mediation analysis was used to analyze the effects of resilience on financial toxicity and quality of life.</p> Results <p>The patients’ average QOL-LC score was 125.41. Univariate analysis revealed that residence, monthly disposable household income, metastasis, China liver cancer staging (CNLC), and number of hospitalizations in the last year were statistically significant factors associated with quality of life. Higher resilience and lower financial toxicity (indicated by a higher COST-PROM score) were both moderately positively correlated with quality of life. Mediation analysis indicated that resilience partially mediated the relationship between financial toxicity and quality of life (mediation effect = 31.2%).</p> Conclusions <p>The resilience exhibited by patients with primary liver cancer may help mitigate the impact of economic pressures on quality of life. Given its cross-sectional design, further validation of this causal pathway will undoubtedly constitute an important avenue for future research.</p>