Background <p>Chemotherapy-induced hiccups are one of the frequently appearing adverse events. Previous reports have suggested that cisplatin (CDDP) combined with dexamethasone and neurokinin 1 (NK1) receptor antagonists is particularly associated with these symptoms. Consequently, we aimed to identify additional factors involved in the development of problematic hiccups during the real-world treatment.</p> Methods <p>Patients with thoracic cancer first receiving CDDP-containing treatment (≥ 75&#xa0;mg/m²) with dexamethasone, palonosetron, and aprepitant were retrospectively assessed (n = 286). The primary endpoint was the evaluation of risk factors for grade ≥ 2 hiccups during the first cycle. Secondary endpoints were the evaluation of factors for all-grade symptoms and the efficacy of rescue medication.</p> Results <p>The incidence of grade ≥ 2 hiccups was 32.9%, with all-grade symptoms of 44.8%. Grade 3 severe hiccups were observed in 5.2% of the patients. Most patients (96.8%) received metoclopramide as first-line treatment, and the efficacy of the first medication was confirmed in 59.6% of patients. Multivariate logistic regression analyses identified male sex, baseline hypoalbuminemia, and concomitant bevacizumab as significant risk factors for grade ≥ 2 problematic hiccups (adjusted odds ratio with 95% confidence interval 10.32 [4.38–24.32], P &lt; 0.0001 for males; 2.41 [1.06–5.50], P = 0.04 for hypoalbuminemia; and 3.42 [1.25–9.36], P = 0.02 for concomitant bevacizumab). Moreover, male sex was identified as a singular risk factor for all-grade symptoms (7.94 [4.14–15.22], P &lt; 0.0001).</p> Conclusion <p>Our study revealed that male sex, hypoalbuminemia, and concomitant bevacizumab use were significant risk factors for clinically problematic hiccups in patients receiving CDDP-containing treatment along with dexamethasone and NK1 receptor inhibitors for thoracic cancer.</p>