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Background: Differential diagnosis of pancreatic solid lesion (PSL) and prognosis of pancreatic cancer (PC) is a clinical challenge. We aimed to explore the differential diagnostic value of sound speed (SS) obtained from endoscopic ultrasonography (EUS) in PSL and the prognostic value of SS in PC. Methods: Patients with PSL in The Third Xiangya Hospital of Central South University from March 2019 to October 2019 were prospectively enrolled, who obtained SS from PSL. Patients were divided into the PC group and the pancreatic benign lesion (PBL) group. SS1 is the SS of lesions and SS2 is the SS of normal tissues adjacent to lesions. Ratio1 is equal to SS1 divided by SS2 of PSL (ratio1 = SS1/SS2). Results: Eighty patients were enrolled (24 PBL patients, 56 PC patients). SS1 and ratio1 in PC group were higher compared with PBL group (SS1:1568.00 vs. 1550.00, Z = −2.066, p = 0.039; ratio1: 1.0110 vs. 1.0051, Z = −3.391, p = 0.001). The SS1 in PC (Z = −6.503, p < 0.001) was higher compared to SS2. In the nonsurgical group of PC, low ratio1 predicted high overall survival (OS) (7.000 months vs. 4.000 months; p = 0.039). In the surgical group of PC, low SS1 was associated with low median OS (4.000 months vs. 12.000 months; p = 0.033). Conclusions: SS plays a vital role in distinguishing between PBL and PC. Higher SS1 and ratio1 obtained by EUS are more related to PC than PBL. In PC patients, high SS1 may predict pancreatic lesions. In the nonsurgical group of PC, low ratio1 may predict high OS. However, in the surgical group of PC, low SS1 may predict low OS. [ABSTRACT FROM AUTHOR]