We aimed to assess the effects of serratus anterior plane block (SAPB) and thoracic paravertebral nerve block (TPVB) on analgesia, immune function and serum tumor markers in patients after thoracoscopic radical resection of lung cancer. A total of 132 patients enrolled from February 2019 to November 2020 were prospectively selected and randomly divided into 3 groups (n=44). Control group received general anesthesia. After induction of general anesthesia, TPVB or SAPB group was given TPVB or SAPB. Their clinical data, operation conditions, Visual Analogue Scale (VAS) score, immune function, serum tumor markers and adverse reactions were compared. TPVB and SAPB groups had lower dosage of sufentanil during operation, later time of first pressing patient-controlled intravenous analgesia (PCA) pump after operation and smaller number of pressing PCA pump within 48 h after operation than those of control group (P<0.05). VAS scores at rest and coughing decreased 6 and 12 h after operation in TPVB and SAPB groups compared with that in control group (P<0.05). Cluster of differentiation 3 (CD3), CD4 and CD4/CD8 ratio were higher, while CD8 was lower 24 and 48 h after operation in TPVB and SAPB groups than those of control group (P<0.05). TPVB and SAPB groups had lower serum tumor marker levels 24 h after operation than those of control group (P<0.05). The three groups had similar incidence rates of adverse reactions (P>0.05). SAPB and TPVB can markedly improve postoperative analgesic effect, enhance immune function and decrease serum tumor marker levels in patients receiving thoracoscopic radical resection of lung cancer, without increasing adverse reactions. However, TPVB may puncture the pleura.