Background: Symptom burden among long-term hemodialysis (HD) patients is high, and addressing symptoms has been identified as a key research priority by patients. Acupressure has shown some effectiveness in management of symptoms in patients with HD. Objective: The purpose of this study was to explore the feasibility and the effect of implementing a self-administered acupressure intervention on symptom burden and quality of life for in-center HD patients. Design: A pilot randomized controlled study. Setting: Two outpatient community HD clinics between in Calgary, Alberta, Canada. Patients or Sample or Participants: Patients on HD for at least 3 months and with at least one symptom score rated greater than moderate were eligible for the study. Methods: Participants were randomized into either the (1) self-acupressure + usual care or (2) usual care alone group. Participants in the acupressure group were given a wooden acupressure tool and taught how to self-administer protocol on 6 acupressure sites for the 4-weeek study duration. Feasibility outcomes were assessed through satisfaction surveys and attrition. Other outcomes included quality of life and symptom scores by validated questionnaires (EQ-5D-5L and Integrated Palliative Outcome Score—Renal [IPOS-Renal]). Results: Thirty-two participants were successfully enrolled in the study; acceptability was high with study completion at 98% in the intervention group and 82% adherence rate to the 4-week protocol. Participants in the intervention group reported an improved change score in quality of life (EQ-5D-5L Index Score change = +0.053; EQ-5D-5L visual analog scale score change = +6.7). Participants in the intervention group also reported improved symptom scores (IPOS-Renal overall change = −2.8). Limitations: Small sample size and intervention duration are limitations of this pilot study. Conclusions: The results from this study suggest that self-acupressure was acceptable and feasible in this sample of HD patients. Self-acupressure may have a role for supporting the management of symptoms in HD patients. These pilot results can be used to inform larger more definitive investigations.