Objective: To investigate the correlation between changes in tumor burden and the dose of intraoperative radiation therapy (IORT) for unresectable pancreatic cancer within 60 days of treatment evaluated using imaging parameters. Methods: A total of 32 cases of unrespectable pancreatic cancer treated with IORT at the Sichuan Cancer Hospital from April 2017 to July 2020 were retrospectively included. The imaging parameters of the tumor were recorded 7 days before IORT and 60 days after IORT: the longest axis (LA), shortest axis (SA), largest cross-sectional area (A), absolute value changes of each parameter (Δ), and change rate (Δ%). Different tumor load groups (shrinking/stabilizing/increasing) were differentiated, and the relationship between each parameter, IORT radiation dose, and tumor response time was analyzed. Results: The LA of unresectable pancreatic cancer after IORT was lower than that before IORT, with significant differences observed. The SA and A values of unresectable pancreatic cancer after IORT were lower than those before IORT, with no statistical significance observed. Based on ΔLA of the pancreatic tumor, the three groups, shrinkage, stability, and enlargement, were divided, with a corresponding tumor response time of (39.57±11.77) d, (38.08±12.87) d, (41.17±42) d, respectively. There were no significant differences in LA, SA, and A among the three groups before IORT, while significant differences were observed in LA, SA, and A after IORT. The ΔLA of the three groups was statistically significant before and after IORT. There was a moderate negative correlation between ΔLA and IORT dose levels in unrespectable pancreatic cancer (r
=−0.47,). There was a moderate and high correlation between ΔLA and IORT dose in the stable group and ΔA and IORT dose in the enlargement group, respectively (r
=0.66 vs. 0.90). There was no significant correlation between the response time and imaging parameters in these groups, except for a moderate negative correlation between ΔSA and response time in the stability group (r
=−0.68). Conclusion: ΔLA can be used to evaluate changes in tumor load within 60 days of IORT for unresectable pancreatic cancer. The efficacy of pancreatic cancer could be correlated with the IORT irradiation dose, whereas the tumor burden could not be affected by the tumor response time.