Background <p>With the prolongation of life expectancy in hepatocellular carcinoma (HCC) patients attributed to the advancement of treatments, the morbidity of second primary malignancies (SPM) has attracted considerable academic attention. The study aimed to probe into the risk and prognostic factors of SPM in HCC survivors.</p> Methods <p>All information about the participants was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The competing risk regression and LASSO regression were adopted to establish a nomogram for SPM prediction. The validity of the nomogram was authenticated by concordance index (C-index), calibration curves, and receiver operating characteristic curves (ROC). Cox regression and Kaplan–Meier curves were utilized for survival analysis of SPM patients.</p> Results <p>A total of 2491 cases were enrolled in the research, with 182 (7.31%) patients developing SPMs in the follow-up duration. The median follow-up time of second primary malignancy patients (67 months) was longer than that of non-second primary malignancy patients (30 months). The nomogram for the occurrence of SPM was created with age, grade, AJCC, chemotherapy and surgery. Covariates such as age, sex, distant tumor stage, surgery, latency and tumor type, had an impact on OS or CSS of SPM patients respectively based on the outcome of survival analysis.</p> Conclusion <p>Our study identified crucial predictive indicators for the risk of SPM in HCC survivors and the prognosis of SPM patients. The nomogram constructed for estimating the probability of SPM performed well. These findings may provide clinicians with meritorious suggestions on surveillance and management of SPMs in HCC patients.</p>