Background: Cancer clinical trial (CCT) participants are at risk for experiencing adverse effects from financial toxicity, yet these remain understudied. We sought to describe associations among CCT participant-reported financial toxicity (financial burden [FB] and trial cost concerns), symptoms, illness perceptions, communication confidence, hospitalizations, and survival. Methods: From 7/2015-7/2017, we prospectively enrolled CCT participants who expressed interest in financial assistance (n = 100) and a patient group matched by age, sex, cancer type, specific trial, and trial phase (n = 98). We assessed FB (burdened by costs of cancer care), trial cost concerns (worried about affording medical costs of a CCT), physical (Edmonton Symptom Assessment Scale [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire [BIPQ]), and communication confidence (Perceived Efficacy in Patient-Physician Interactions [PEPPI]). We used regression models to explore sociodemographic associations with FB and trial cost concerns, as well as their associations with symptom burden, illness perceptions, and communication confidence, adjusting for age, sex, race, performance status, marital status, and metastatic status. We also used Kaplan-Meier and regression methods to evaluate their associations with 6-month hospitalizations and survival. Results: Of 198 patients enrolled, 112 (56.6%) reported FB and 82 (41.4%) had trial cost concerns. Patients with FB were younger (OR 0.96, 95% CI 0.94-0.98) with lower incomes (< $100,000, OR 4.61, 95% CI 2.35-9.01). Patients with trial cost concerns had lower incomes (< $100,000, OR 2.78, 95% CI 1.45-5.29). On adjusted analyses, patients with FB had higher ESAS (OR 1.03, 95% CI 1.02-1.05), PHQ-4 depression (OR 1.54, 95% CI 1.22-1.94), and PHQ-4 anxiety (OR 1.30, 95% CI 1.08-1.55) scores, as well as more negative illness perceptions (OR 1.04, 95% CI 1.01-1.07), but no significant difference in communication confidence (OR 0.98, 95% CI 0.93-1.05). Patients reporting trial cost concerns had higher ESAS (OR 1.03, 95% CI 1.01-1.05), PHQ-4 depression (OR 1.35, 95% CI 1.10-1.65), and PHQ-4 anxiety (OR 1.27, 95% CI 1.07-1.51) scores, as well as more negative illness perceptions (OR 1.06, 95% CI 1.03-1.10), and lower communication confidence (OR 0.93, 95% CI 0.87-0.99). Financial toxicity was not significantly associated with hospitalizations or survival. Conclusions: In this study of CCT participants, younger patients with lower incomes were most vulnerable to financial toxicity. Financial toxicity was associated with greater symptoms, more negative illness perceptions, and lower communication confidence, underscoring the importance of addressing these issues when seeking to alleviate the adverse effects of financial toxicity in CCT participants.