Abstract Background Anxiety is a common symptom experienced by patients with cancer, who are increasingly interested in non-pharmacologic symptom management. Acupressure, a noninvasive intervention thought to impact the neurohormonal axis, has shown promise in reducing anxiety. However, research on acupressure for anxiety in patients with cancer has been limited. Methods Individuals receiving chemotherapy, who reported baseline anxiety, were eligible for this study. Consenting participants received one 15-minute nurse-led acupressure session and completed pre- and post-intervention surveys. The primary endpoint was a change in anxiety. Participants were also asked about symptoms of nausea, pain, well-being, relaxation, worry, and distress. Participants were invited to learn self-acupressure techniques. These participants were asked to complete a final survey 1-week post-intervention. Results Thirty adult patients participated in this study. Mean baseline anxiety was 5 on a 0 to 10 Likert scale. Immediate post-intervention anxiety scores significantly improved for all thirty patients to an average of 2.0 (P < .001). Mean nausea scores improved from 1.5 at baseline to 0 post-intervention (P < .001), and pain scores improved from 2.0 at baseline to 1.0 post-intervention (P = .001). Participants reported significant improvement in sense of wellbeing (P = .0004), distress (P < .001), ability to achieve relaxation (P < .001), and ability to control their worries (P < .001). The improvement in anxiety, well-being, and relaxation was sustained at one week. 100% of participants stated that they would recommend acupressure for symptom management. Conclusion Acupressure is a promising non-pharmacologic intervention for the management of cancer-associated anxiety.