Objective To compare the effectiveness of Valsalva maneuver and compound lidocaine cream in relieving pain during non-invasive needle insertion into the totally implantable access port. Methods A total of 148 patients treated with antineoplastic drugs were conveniently enrolled, and randomized to received any of the 3 interventions for non-invasive needle insertion into the port:applying medical Vaseline as placebo (the control group) or compound lidocaine cream (the lidocaine group) 1 hour before puncture, or asking the patients to breathe with Valsalva maneuver (the Valsalva group) upon puncture.Pain scores during needle insertion were measured and compared. Results The lidocaine group had the lowest pain scores as compared with the other two groups (all P＜0.05). Conclusion Use of compound lidocaine cream could alleviate pain during non-invasive needle insertion into the totally implantable access port, and enhance overall comfort of patients.