Background: Prior research suggests that autonomic modulation investigated by heart rate variability (HRV) might act as a novel predictive biomarker for cancer prognosis, such as in breast cancer and pancreatic cancer. It is not clear whether there is a correlation between autonomic modulation and prognosis in patients with extensive-stage small cell lung cancer (ES-SCLC). Therefore, the purpose of the study was to examine the association between short-term HRV, deceleration capacity (DC) and acceleration capacity (AC) of heart rate and overall survival in patients with ES-SCLC. Methods: We recruited 40 patients with ES-SCLC, and 39 were included in the final analysis. A 5-min resting electrocardiogram of patients with ES-SCLC was collected using a microelectrocardiogram recorder to analyse short-term HRV, DC and AC. The following HRV parameters were used: standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD). Overall survival of patients with ES-SCLC was defined as time from the date of electrocardiogram measurement to the date of death or the last follow-up. Follow-up was last performed on 07 June 2023. There was a median follow-up time of 42.2 months. Results: Univariate analysis revealed that the HRV parameter SDNN, as well as DC significantly predicted the overall survival of ES-SCLC patients (all p < 0.05). Multivariate analysis showed that the HRV parameters SDNN (hazard ratio = 5.254, 95% CI: 1.817-15.189, p = 0.002), RMSSD (hazard ratio = 3.024, 95% CI: 1.093-8.372, p = 0.033), as well as DC (hazard ratio = 3.909, 95% CI: 1.353-11.293, p = 0.012) were independent prognostic factors in ES-SCLC patients. Conclusion: Decreased HRV parameters (SDNN, RMSSD) and DC are independently associated with shorter overall survival in ES-SCLC patients. Autonomic nervous system function (assessed based on HRV and DC) may be a new biomarker for evaluating the prognosis of patients with ES-SCLC.