Objective To explore the correlation between malignant tumors and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Methods A total of 336 patients with malignant tumors (cancer group) who were admitted to the Department of Cardiology, Chinese PLA General Hospital and underwent coronary angiography from January 1, 2009 to December 31, 2020, and were newly diagnosed and had not received any anti-tumor treatment were selected. They were matched with 1 008 patients (non-cancer group) in a 1∶3 ratio using propensity score matching based on gender and age. Clinical data of the patients were collected, including age, gender, serum NT-proBNP, left ventricular ejection fraction (LVEF), SYNTAX score, serum creatinine, and tumor diagnosis information. The patients were divided into 4 groups based on the quartiles of NT-proBNP levels: low-level group (NT-proBNP≤61.80 pg/mL), medium-level group (61.80 pg/mL＜NT-proBNP≤152.95 pg/mL), high-level group (152.95 pg/mL＜NT-proBNP≤470.10 pg/mL), and very high-level group (NT-proBNP＞470.10 pg/mL). Ordered logistic regression analysis was used to analyze the correlation between malignant tumors and serum NT-proBNP. Results A total of 1 344 patients were included, with an average age of (65.78±9.18) years old, 1 003 males (74.63%), LVEF of 60.00% (55.00%, 64.00%) , SYNTAX score of (13.84±11.63) points, and creatinine level of 76.60 (66.50, 88.88) μmol/L. Among the 336 cancer patients, the top 3 types of cancer were lung cancer (84 cases, 25.00%), colorectal cancer (58 cases, 17.26%), and gastric cancer (52 cases, 15.48%). The NT-proBNP levels in the cancer group were significantly higher than those in the non-cancer group (208.45[85.75, 601.83] pg/mL vs 134.35[57.18, 430.23] pg/mL, P＜0.001). Ordered logistic regression analysis showed that in the unadjusted model, malignant tumors were significantly associated with higher NT-proBNP levels (OR＝1.561, 95% CI 1.538-1.584, P＜0.001); after adjusting for relevant factors, malignant tumors remained significantly associated with higher serum NT-proBNP levels (OR＝1.384, 95% CI 1.070-1.791, P＝0.013). Conclusions NT-proBNP in malignant tumor patients is higher than that in non-malignant tumor patients, and there is a significant correlation between malignant tumors and serum NT-proBNP levels.