The correlations between early responses and the variations in physical density and primary tumor volume (TV) according to cone-beam computed tomography (CBCT) during chemoradiotherapy for non-small cell lung cancer (NSCLC) patients were investigated. 54 patients with inoperable and locally advanced NSCLC were included in this study. The CT numbers (CTN) and TV were measured on each of the seven observation points. The changes in the mean CTN values and the variation ratios of TV during the treatment course were analysed and correlated with the clinical outcomes, as evaluated by the RECIST criteria. For patients who responded to treatment, the CTN and TV change ratio decreased by 28.44 ± 13.12 HU and 32.01% (range, 8.46-61.67%); these values were significantly higher than those in the non-responding patients, with 19.63 ± 8.67 HU and 23.20% (range, -15.57-38%) (p = 0.016, p = 0.048), respectively. The area under curve for the combination of CTN and TV was larger than either alone (AUC = 0.751, p = 0.002). The differences between response and non-response were most significant between Fraction 10 and Fraction 15 for CTN changes and between Fraction 5 and Fraction 10 for the TV regression ratio. The changes in CTN and TV obtained from CBCT images have the potential capability to predict an early response of NSCLC.