Objectives. Our study will investigate the effect of ultrasound-guided thoracic paravertebral block (UG-TPVB) on postoperative pain, quality of life, and enhanced recovery in patients with non-small-cell lung cancer (NSCLC) undergoing lobectomy surgery. Methods. Our study included 100 patients aged 52 to 75 years who underwent lobectomy surgery with pathological diagnosis of NSCLC. Patients received ultrasound-guided thoracic paravertebral block or general anesthesia with tracheal intubation. Patients’ pain score was recorded on a numeric rating scale (NRS) 24 hours post operation. The total postoperative dosage of tramadol hydrochloride, length of hospitalization, quality of life (QoL), and inflammation levels were recorded. Results. Compared with patients who received general anesthesia with tracheal intubation, patients in the UG-TPVB group had lower postoperative NRS scores at 24 h (1.8 vs. 3.5,
P
=
0.035
); the average 24 h postoperative NRS score of the UG-TPVB group is lower than that of the general anesthesia with tracheal intubation (4.6 vs. 5.3,
P
=
0.012
), thus receiving less dosage of tramadol hydrochloride (
221
±
45
vs.
250
±
38
mg,
P
<
0.01
). Patients in the UG-TPVB group had better EORTC QLQ-C30 scores compared with patients in the general anesthesia with tracheal intubation group. The difference of length of hospitalization, hs-CRP, and IL-6 between two groups did not reach statistical difference (length of hospitalization 6.2 vs. 6.9 days,
P
=
0.055
; hs-CRP:
7.1
±
1.9
vs.
10.4
±
6.6
,
P
=
0.095
; and IL-6:
71.3
±
7.2
vs.
68.9
±
8.7
,
P
=
0.529
). Discussion. NSCLC patients undergoing lobectomy surgery who received UG-TPVB had less postoperative pain, used less dosage of tramadol hydrochloride, and had better QoL.