Drowsy driving accidents can be prevented if predicted in advance. The present work aims to develop a new method for detecting driver drowsiness based on the fact that the autonomic nervous function affects heart rate variability (HRV), which is a fluctuation of the RR interval (RRI) obtained from an electrocardiogram (ECG). The proposed method uses eight HRV features derived through HRV analysis as input variables of multivariate statistical process control (MSPC), which is a well-known anomaly detection method in the field of process control. In the proposed method, only one principal component was adopted in MSPC and driver drowsiness was detected through monitoring the T2 statistic. Driving simulator experiments demonstrated that driver drowsiness was successfully detected in seven out of eight cases before accidents occurred. In addition, the proposed method was implemented in a smartphone app for on-vehicle use.